{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:01:15Z","timestamp":1776322875673,"version":"3.50.1"},"reference-count":138,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor cells by the immune system, thereby diminishing tumor immunity. The argument for employing epigenetic drugs in the treatment of acute myeloid leukemia (AML) patients is supported by evidence that both epigenetic changes and mutations in the epigenetic machinery contribute to AML etiology. Although hypomethylating drugs have been licensed for use in AML, additional epigenetic inhibitors, such as HDACis, are now being tested in humans. Preclinical studies evaluating the efficacy of HDACis against AML have shown the ability of specific agents, such as anobinostat, vorinostat, and tricostatin A, to induce growth arrest, apoptosis, autophagy and cell death. However, these inhibitors do not seem to be successful as monotherapies, but instead achieve results when used in conjunction with other medications. In this article, we discuss the mounting evidence that HDACis promote extensive histone acetylation, as well as substantial increases in reactive oxygen species and DNA damage in hematological malignant cells. We also evaluate the potential of various natural product-based HDACis as therapeutic agents to combat hematological malignancies.<\/jats:p>","DOI":"10.3390\/cancers15102808","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T07:03:58Z","timestamp":1684393438000},"page":"2808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-1617","authenticated-orcid":false,"given":"Dilipkumar","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495 009, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushboo","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495 009, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyam Sundar","family":"Nandi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Indian Council for Medical Research-National Institute of Virology, Mumbai 400 012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surajit","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Mishra","sequence":"additional","affiliation":[{"name":"Aurobindo Pharma, Durham, NC 27703, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-4618","authenticated-orcid":false,"given":"Arijit","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences and Research, Balisha 743 234, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2375-6612","authenticated-orcid":false,"given":"Ricardo","family":"Lagoa","sequence":"additional","affiliation":[{"name":"Associate Laboratory in Chemical Engineering, Polytechnic Institute of Leiria, Morro do Lena, Alto do Vieiro, 2411-901 Leiria, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-200X","authenticated-orcid":false,"given":"Jack T.","family":"Burcher","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-960X","authenticated-orcid":false,"given":"Anupam","family":"Bishayee","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1517\/14728221003796609","article-title":"Class I histone deacetylases 1, 2 and 3 are highly expressed in classical Hodgkin\u2019s lymphoma","volume":"14","author":"Adams","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.tips.2017.05.009","article-title":"Interstrand crosslink repair as a target for HDAC inhibition","volume":"38","author":"Nikolova","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a026831","DOI":"10.1101\/cshperspect.a026831","article-title":"HDACs and HDAC inhibitors in cancer development and therapy","volume":"6","author":"Li","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2174\/1568026619666190603092407","article-title":"Recent study of dual HDAC\/PARP inhibitor for the treatment of tumor","volume":"19","author":"Lu","year":"2019","journal-title":"Curr. Top Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41580-018-0081-3","article-title":"Functions and Mechanisms of Non-Histone Protein Acetylation","volume":"20","author":"Narita","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/B978-0-12-394387-3.00003-3","article-title":"HDAC inhibitors: Roles of DNA damage and repair","volume":"116","author":"Robert","year":"2012","journal-title":"Adv. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11700","DOI":"10.1073\/pnas.182372299","article-title":"The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin","volume":"99","author":"Butler","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Bishayee, A., and Pandey, A.K. (2018). Targeting histone deacetylases with natural and synthetic agents: An emerging anti-cancer strategy. Nutrients, 10.","DOI":"10.3390\/nu10060731"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bouyahya, A., El Hachlafi, N., Aanniz, T., Bourais, I., Mechchate, H., Benali, T., Shariati, M.A., Burkov, P., Lorenzo, J.M., and Wilairatana, P. (2022). Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates. Molecules, 27.","DOI":"10.3390\/molecules27082568"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ruzic, D., Djokovi\u0107, N., Srdi\u0107-Raji\u0107, T., Echeverria, C., Nikolic, K., and Santibanez, J.F. (2022). Targeting histone deacetylases: Opportunities for cancer treatment and chemoprevention. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010209"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"547","DOI":"10.2147\/DDDT.S110264","article-title":"Defective DNA repair mechanisms in prostate cancer: Impact of olaparib","volume":"11","author":"Tombolini","year":"2017","journal-title":"Drug Des Devel Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1101\/gad.284109.116","article-title":"Epigenetics of hematopoiesis and hematological malignancies","volume":"30","author":"Hu","year":"2016","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129305","DOI":"10.1016\/j.bmcl.2023.129305","article-title":"Design, synthesis, and biological evaluation of novel HDAC inhibitors with a 3-(benzazol-2-yl) quinoxaline framework","volume":"88","author":"Yang","year":"2023","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s13659-020-00293-7","article-title":"Natural products in cancer therapy: Past, present and future","volume":"11","author":"Huang","year":"2021","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.clnu.2013.03.008","article-title":"Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy","volume":"32","author":"Lecumberri","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3389\/fchem.2022.948217","article-title":"Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer","volume":"10","author":"Pramanik","year":"2022","journal-title":"Front. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"946811","DOI":"10.3389\/fphar.2022.946811","article-title":"Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: Fundamentals and beyond","volume":"13","author":"Feng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bioorg.2017.12.007","article-title":"Design, synthesis and evaluation of novel N-hydroxybenzamides\/N-hydroxypropenamides incorporating quinazolin-4 (3H)-ones as histone deacetylase inhibitors and antitumor agents","volume":"76","author":"Hieu","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.4314\/tjpr.v15i7.8","article-title":"Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line","volume":"15","author":"Saha","year":"2016","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Garc\u00eda, S., Mercado-S\u00e1nchez, I., Bahena, L., Alcaraz, Y., Garc\u00eda-Revilla, M.A., Robles, J., Santos-Mart\u00ednez, N., Ordaz-Rosado, D., Garc\u00eda-Becerra, R., and Vazquez, M.A. (2020). Design of fluorescent coumarin-hydroxamic acid derivatives as inhibitors of HDACs: Syn-thesis, anti-proliferative evaluation and docking studies. Molecules, 25.","DOI":"10.3390\/molecules25215134"},{"key":"ref_21","first-page":"5325","article-title":"Green Tea Polyphenol Epigallocatechin 3-Gallate, Contributes to the Degradation of DNMT3A and HDAC3 in HCT 116 Human Colon Cancer Cells","volume":"33","author":"Moseley","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1158\/1940-6207.CAPR-11-0009","article-title":"A Novel Prodrug of Epigallocatechin-3-Gallate: Differential Epigenetic HTERT Repression in Human Breast Cancer Cells","volume":"4","author":"Meeran","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/mc.20866","article-title":"Plant Flavone Apigenin Inhibits HDAC and Remodels Chromatin to Induce Growth Arrest and Apoptosis in Human Prostate Cancer Cells: In Vitro and in Vivo Study","volume":"51","author":"Pandey","year":"2012","journal-title":"Mol. Carcinog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neuroscience.2015.02.054","article-title":"Galangin-Induced down-Regulation of BACE1 by Epigenetic Mechanisms in SH-SY5Y Cells","volume":"294","author":"Zeng","year":"2015","journal-title":"Neuroscience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/apm.12906","article-title":"Epigenetic therapy in hematological cancers","volume":"127","author":"Dimopoulos","year":"2019","journal-title":"Apmis"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Serrano, M., Winkler, R., Santos, J.C., Le Pann\u00e9rer, M.M., Buschbeck, M., and Rou\u00e9, G. (2022). Histone modifications and their targeting in lymphoid malignancies. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202111.0317.v1"},{"key":"ref_27","unstructured":"Rathinavelu, A., and Natarajan, U. (2023). Epigenetics in Organ Specific Disorders, Academic Press."},{"key":"ref_28","unstructured":"Andrade, M.B. (2023, April 29). The Role of Epigenetics in Glioblastoma\u2014A Meta Analysis. Available online: https:\/\/repositorio-aberto.up.pt\/bitstream\/10216\/130224\/2\/429915.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.canlet.2017.12.030","article-title":"Pan-HDAC inhibition by panobino-stat medi-ates chemosensi-tization to carboplatin in non-small cell lung cancer via at-tenuation of EGFR signaling","volume":"417","author":"Wang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1517\/13543784.2013.815165","article-title":"Panobinostat in lymphoid and myeloid malignancies","volume":"22","author":"Khot","year":"2013","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_31","first-page":"2052","article-title":"Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors","volume":"29","author":"Giaccone","year":"2011","journal-title":"Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s13277-012-0544-7","article-title":"Induction of apoptosis by Trichostatin A in human breast cancer cell lines: Involvement of 15-Lox-1","volume":"34","author":"Salimi","year":"2013","journal-title":"Tumor Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxlet.2013.05.643","article-title":"MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells","volume":"221","author":"Liu","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.lungcan.2004.03.002","article-title":"Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer","volume":"45","author":"Reid","year":"2004","journal-title":"Clin. Lung Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1358\/dof.2007.032.01.1052960","article-title":"Combination therapy with valproic acid in cancer: Initial clinical approach","volume":"32","author":"McIntyre","year":"2007","journal-title":"Drugs Future"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.2217\/fon-2016-0526","article-title":"Entinostat: A promising treatment option for patients with advanced breast cancer","volume":"13","author":"Connolly","year":"2017","journal-title":"Future Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Saito, Y., Mizokami, A., Izumi, K., Naito, R., Goto, M., and Nakagawa-Goto, K. (2021). \u03b1-Trifluoromethyl chalcones as potent anticancer agents for androgen receptor-independent prostate cancer. Molecules, 26.","DOI":"10.3390\/molecules26092812"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/CAD.0000000000000040","article-title":"Histone deacetylase inhibitors: An overview of the clinical studies in solid tumors","volume":"25","author":"Slingerland","year":"2014","journal-title":"Anticancer. Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1097\/PAS.0b013e31816b6478","article-title":"SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma","volume":"32","author":"Jang","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer dissocia-tion","volume":"421","author":"Bakkenist","year":"2003","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1158\/1541-7786.MCR-06-0111","article-title":"Histone deacetylase inhibitors (HDI) cause DNA damage in leukemia cells: A mechanism for leukemia-specific HDI-dependent apoptosis?","volume":"4","author":"Gaymes","year":"2006","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/ncb2344","article-title":"More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance","volume":"13","author":"Lukas","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Da\u015bko, M., de Pascual-Teresa, B., Ort\u00edn, I., and Ramos, A. (2022). HDAC inhibitors: Innovative strategies for their design and applications. Molecules, 27.","DOI":"10.3390\/molecules27030715"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrm2651","article-title":"The emerging role of nuclear architecture in DNA repair and genome maintenance","volume":"10","author":"Misteli","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101312","DOI":"10.1016\/j.tranon.2021.101312","article-title":"HDAC inhibitors: Targets for tumor therapy, immune modulation and lung diseases","volume":"16","author":"Shanmugam","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"114944","DOI":"10.1016\/j.bcp.2022.114944","article-title":"Combinatorial strategies to potentiate the efficacy of HDAC inhibitors in fusion-positive sarcomas","volume":"198","author":"Lanzi","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.1093\/emboj\/cdf616","article-title":"MDM2\u2013HDAC1-mediated deacetylation of p53 is required for its degradation","volume":"21","author":"Ito","year":"2002","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrd772","article-title":"Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer","volume":"1","author":"Johnstone","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15741","DOI":"10.1074\/jbc.M513172200","article-title":"The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM","volume":"281","author":"Jiang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/B978-0-12-385493-3.00005-X","article-title":"Assessment of oxidative stress-induced DNA damage by immunoflourescent analysis of 8-oxodG","volume":"103","author":"Lee","year":"2011","journal-title":"Methods Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1158\/1535-7163.MCT-10-1108","article-title":"Carfilzomib Interacts Synergistically with Histone Deacetylase Inhibitors in Mantle Cell Lymphoma Cells In Vitro and In VivoCarfilzomib and Vorinostat in Mantle Cells","volume":"10","author":"Dasmahapatra","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/bs.acr.2018.02.006","article-title":"Advances and Challenges of HDAC inhibitors in cancer therapeutics","volume":"138","author":"McClure","year":"2018","journal-title":"Adv. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1128\/MCB.25.13.5429-5444.2005","article-title":"Blockade of histone deacetylase inhibitor-induced RelA\/p65 acetylation and NF-\u03baB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation","volume":"25","author":"Dai","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9558","DOI":"10.1074\/jbc.M808906200","article-title":"Human CtIP mediates cell cycle control of DNA end resection and double strand break repair","volume":"284","author":"Huertas","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"114049","DOI":"10.1016\/j.ejmech.2021.114049","article-title":"Design and synthesis of HDAC inhibitors to enhance the therapeutic effect of diffuse large B-cell lymphoma by improving metabolic stability and pharmacokinetic characteristics","volume":"22","author":"Cui","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12460","DOI":"10.1021\/acs.jmedchem.0c00830","article-title":"Thirty years of HDAC inhibitors: 2020 insight and hindsight","volume":"63","author":"Ho","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1080\/13543776.2020.1725470","article-title":"Histone deacetylase (HDAC) inhibitors in cancer: A patent review (2017-present)","volume":"30","author":"Zhao","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_58","first-page":"3451","article-title":"Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages","volume":"101","author":"Rahman","year":"2003","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/bjc.2011.532","article-title":"Differential response of cancer cells to HDAC inhibitors trichostatin A and depsipeptide","volume":"106","author":"Chang","year":"2012","journal-title":"BJC"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e202100755","DOI":"10.1002\/cmdc.202100755","article-title":"Balancing Histone Deacetylase (HDAC) Inhibition and Drug-likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors","volume":"17","author":"Haschemi","year":"2022","journal-title":"Chem. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1074\/jbc.M507712200","article-title":"DNA damage promotes histone deacetylase 4 nuclear localization and repression of G2\/M promoters, via p53 C-terminal lysines","volume":"281","author":"Basile","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd2133","article-title":"Anticancer activities of histone deacetylase inhibitors","volume":"5","author":"Bolden","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1021\/acschembio.7b00942","article-title":"Histone deacetylase 11 is a fatty-acid deac-ylase","volume":"13","author":"Kutil","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/35088000","article-title":"Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair","volume":"412","author":"Walker","year":"2001","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0092-8674(93)90057-W","article-title":"The DNA-dependent protein kinase: Requirement for DNA ends and association with Ku antigen","volume":"72","author":"Gottlieb","year":"1993","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4161\/epi.1.3.2896","article-title":"The epigenetic modifier, valproic acid, enhances radiation sensitivity","volume":"1","author":"Karagiannis","year":"2006","journal-title":"Epigenetics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14639","DOI":"10.1073\/pnas.1008522107","article-title":"Histone deacetylase inhibitor induces DNA damage, which normal but nottransformed cells can repair","volume":"107","author":"Lee","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kachhap, S.K., Rosmus, N., Collis, S.J., Kortenhorst, M.S., Wissing, M.D., Hedayati, M., Shabbeer, S., Mendonca, J., Deangelis, J., and Marchionni, L. (2010). Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011208"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"930","DOI":"10.4161\/cc.9.5.10931","article-title":"Tip60: Connecting chromatin to DNA damage signaling","volume":"9","author":"Sun","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1128\/MCB.01476-09","article-title":"MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair","volume":"30","author":"Sharma","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1038\/emboj.2010.188","article-title":"Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4","volume":"29","author":"Polo","year":"2010","journal-title":"EMBOJ"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Petruccelli, L.A., Dup\u00e9r\u00e9-Richer, D., Pettersson, F., Retrouvey, H., Skoulikas, S., and Miller, W.H. (2011). Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020987"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nature06337","article-title":"Human CtIP promotes DNA end resection","volume":"450","author":"Sartori","year":"2007","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.ccr.2011.12.029","article-title":"Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells","volume":"21","author":"Tsai","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_75","first-page":"1","article-title":"Epigenetic regulators as promising targets in acute myeloid leukemia therapy","volume":"5","author":"Shao","year":"2020","journal-title":"Signal Transduct. Target The.r"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bbagrm.2010.06.003","article-title":"Inhibitors to understand molecular mechanisms of NAD+-dependent deacetylases (sirtuins)","volume":"1799","author":"Lawson","year":"2010","journal-title":"Biochim. Et Biophys. Acta (BBA)-Gene Regul. Mech."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"San Jos\u00e9-En\u00e9riz, E., Gimenez-Camino, N., Agirre, X., and Prosper, F. (2019). HDAC inhibitors in acute myeloid leukemia. Cancers, 11.","DOI":"10.3390\/cancers11111794"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1038\/leu.2009.182","article-title":"The synergy of panobinostat plus doxorubicin in acute myeloid leukemia suggests a role for HDAC inhibitors in the control of DNA repair","volume":"23","author":"Maiso","year":"2009","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"119504","DOI":"10.1016\/j.lfs.2021.119504","article-title":"Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy","volume":"277","author":"Ramaiah","year":"2021","journal-title":"Life Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10860","DOI":"10.1073\/pnas.95.18.10860","article-title":"ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR\/mSin3\/HDAC1 complex","volume":"95","author":"Wang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1158\/1078-0432.CCR-15-0033","article-title":"Aurora A Kinase Inhibition Selectively Synergizes with Histone Deacetylase Inhibitor through Cytokinesis Failure in T-cell LymphomaAlisertib Synergizes with Romidepsin in TCL","volume":"21","author":"Zullo","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng.2873","article-title":"Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas","volume":"46","author":"Palomero","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_83","first-page":"60","article-title":"The Aurora kinase family in cell division and cancer","volume":"1786","author":"Vader","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/bjh.13566","article-title":"The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma","volume":"171","author":"Marchi","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1586\/era.10.88","article-title":"Romidepsin: A new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors","volume":"10","author":"Grant","year":"2010","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.drudis.2021.08.004","article-title":"Vorinostat in autophagic cell death: A critical insight into autopha-gy-mediated,-associated and-dependent cell death for cancer prevention","volume":"27","author":"Patra","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mrakovcic, M., Bohner, L., Hanisch, M., and Fr\u00f6hlich, L.F. (2018). Epigenetic targeting of autophagy via HDAC inhibition in tumor cells: Role of p53. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123952"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1158\/0008-5472.CAN-05-3617","article-title":"Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes","volume":"66","author":"Heltweg","year":"2006","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"38837","DOI":"10.1074\/jbc.M106779200","article-title":"Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening","volume":"276","author":"Grozinger","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"15113","DOI":"10.1073\/pnas.261574398","article-title":"Identification of a small molecule inhibitor of Sir2p","volume":"98","author":"Bedalov","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e670","DOI":"10.1016\/S2352-3026(22)00165-X","article-title":"The epidemiological landscape of multiple myeloma: A global cancer registry estimate of disease burden, risk factors, and temporal trends","volume":"9","author":"Huang","year":"2022","journal-title":"Lancet Haematol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.1158\/1078-0432.CCR-03-0561","article-title":"Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors","volume":"10","author":"Pei","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ctrv.2015.04.003","article-title":"The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies: A review of clinical studies","volume":"43","author":"Duvic","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1182\/blood-2002-11-3514","article-title":"Molecular sequelae of histone deacetylase inhibition in human malignant B cells","volume":"101","author":"Mitsiades","year":"2003","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0092-8674(03)00939-5","article-title":"The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress","volume":"115","author":"Kawaguchi","year":"2003","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1158\/1078-0432.CCR-16-2526","article-title":"Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple MyelomaRicolinostat, Bortezomib, and Dexamethasone for Mye-loma","volume":"23","author":"Vogl","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_97","first-page":"184-e366","article-title":"First-in-Class Selective HDAC6 Inhibitor (ACY-1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma","volume":"26","author":"Amengual","year":"2021","journal-title":"J. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e85061","DOI":"10.1172\/jci.insight.85061","article-title":"Histone deacetylase inhibitor panobinostat induces calcineurin degradation in multiple myeloma","volume":"1","author":"Imai","year":"2016","journal-title":"JCI Insight"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2533\/chimia.2022.448","article-title":"Current HDAC Inhibitors in Clinical Trials","volume":"76","author":"Noce","year":"2022","journal-title":"Chimia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1182\/blood-2011-06-362434","article-title":"Histone deacetylaseinhibitors are potent inducers of gene expression in latent EBVand sensitize lymphoma cells to nucleoside antiviral agents","volume":"119","author":"Ghosh","year":"2012","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11010-014-2096-1","article-title":"Berberine diminishes side population and down regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA sssPaCa-2. Mol","volume":"394","author":"Park","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tiv.2016.06.004","article-title":"Berberine Acts as a Putative Epigenetic Modulator by Affecting the Histone Code","volume":"36","author":"Wang","year":"2016","journal-title":"Toxicol. In Vitro"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s10142-022-00880-6","article-title":"Discovery of the oncogenic MDM2, a direct binding target of berberine and a potential therapeutic, in multiple myeloma","volume":"22","author":"Li","year":"2022","journal-title":"Funct. Integr. Genom."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Moghadam, E.R., Ang, H.L., Asnaf, S.E., Zabolian, A., Saleki, H., Yavari, M., Esmaeili, H., Zarrabi, A., Ashrafizadeh, M., and Kumar, A.P. (2020). Broad-spectrum preclinical antitumor activity of chrysin: Current trends and future perspectives. Biomolecules, 10.","DOI":"10.3390\/biom10101374"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"458","DOI":"10.2174\/1389450122666211005113234","article-title":"Promising protective effects of chrysin in cardiometabolic diseases","volume":"23","author":"Talebi","year":"2022","journal-title":"Curr. Drug Targets"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/ptr.6869","article-title":"Plant flavone Chrysin as an emerging histone deacetylase inhibitor for prosperous epigenetic-based anticancer therapy","volume":"35","author":"Ganai","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2174\/1389450118666170112130151","article-title":"Designing isoform-selective inhibitors against classical HDACs for effective anticancer therapy: Insight and perspectives from in Silico","volume":"19","author":"Ganai","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Murthy, H.N., and Yadav, G.G. (2021). Gums, Resins and Latexes of Plant Origin: Chemistry, Biological Activities and Uses, Springer International Publishing.","DOI":"10.1007\/978-3-030-76523-1"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"112577","DOI":"10.1016\/j.biopha.2021.112577","article-title":"HDAC inhibitor cowanin extracted from G. fusca induces apoptosis and autophagy via inhibition of the PI3K\/Akt\/mTOR pathways in Jurkat cells","volume":"147","author":"Punpai","year":"2022","journal-title":"Biomed. Pharmacother"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.4103\/0973-1296.176115","article-title":"Cytotoxic properties and complete nuclear magnetic resonance assignment of isolated xanthones from the root of Garcinia cowa Roxb","volume":"12","author":"Wahyuni","year":"2016","journal-title":"Pharmacogn. Mag."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"13017","DOI":"10.1007\/s13277-016-5183-y","article-title":"Molecular targets of curcumin for cancer therapy: An updated review","volume":"37","author":"Kasi","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/jcrt.JCRT_1017_20","article-title":"The golden spice curcumin in cancer: A perspective on finalized clinical trials during the last 10 years","volume":"18","author":"Arslan","year":"2022","journal-title":"J. Cancer Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1745-7254.2005.00081.x","article-title":"Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation","volume":"26","author":"Liu","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1016\/j.bmcl.2004.02.062","article-title":"Three new cyclostellettamines, which inhibit histone deacetylase, from a marine sponge of the genus Xestospongia","volume":"14","author":"Oku","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Wang, K.C., Lu, M.C., Hsu, K.C., El-Shazly, M., Shih, S.P., Lien, S.T., Kuo, F.W., Yang, S.C., Chen, C.L., and Yang, Y.C. (2021). The an-tileukemic effect of xestoquinone, a marine-derived polycyclic quinone-type metabolite, is mediated through ros-induced inhibition of hsp-90. Molecules, 26.","DOI":"10.3390\/molecules26227037"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cbi.2015.10.014","article-title":"Ginsenoside 20 (s)-Rh2 as potent natural histone deacetylase inhibitors suppressing the growth of human leukemia cells","volume":"242","author":"Liu","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_117","first-page":"264","article-title":"Pharmacological and medical applications of Panax ginseng and ginsenosides: A review for use in cardiovascular diseases","volume":"42","author":"Kim","year":"2018","journal-title":"JGR"},{"key":"ref_118","first-page":"126","article-title":"20(S)-Ginsenoside Rh2 induces apoptosis and differentiation of K562 leukemia cells","volume":"194","author":"Chen","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.3390\/md13053132","article-title":"Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxi-dative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities","volume":"13","author":"Shih","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Luparello, C., Mauro, M., Arizza, V., and Vazzana, M. (2020). Histone deacetylase inhibitors from marine invertebrates. Biology, 9.","DOI":"10.3390\/biology9120429"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1021\/jm100244y","article-title":"Synthesis and biological char-acterization of the histone deacetylase inhibitor largazole and C7-modified analogues","volume":"53","author":"Souto","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Emma, M.R., Augello, G.D., Stefano, V., Azzolina, A., Giannitrapani, L., Montalto, G., Cervello, M., and Cusimano, A. (2021). Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031234"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Juli, G., Oliverio, M., Bellizzi, D., Gallo Cantafio, M.E., Grillone, K., Passarino, G., Colica, C., Nardi, M., Rossi, M., and Procopio, A. (2019). Anti-tumor activity and epigenetic impact of the polyphenol oleacein in multiple myeloma. Cancers, 11.","DOI":"10.3390\/cancers11070990"},{"key":"ref_124","first-page":"1287","article-title":"Phenylhexyl isothiocyanate inhibits histone deacetylases and remodels chromatins to induce growth arrest in human leukemia cells","volume":"28","author":"Ma","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3892\/or.2017.5675","article-title":"The blueberry component pterostilbene has potent anti-myeloma activity in bortezomib-resistant cells","volume":"38","author":"Chen","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/mnfr.201000067","article-title":"Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells","volume":"54","author":"Chen","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1016\/j.jss.2011.09.054","article-title":"Pterostilbene and cancer: Current review","volume":"173","author":"McCormack","year":"2012","journal-title":"J. Surg Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.3390\/molecules27082498","article-title":"Health benefits of quercetin in age-related diseases","volume":"27","author":"Maurya","year":"2022","journal-title":"Molecules"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13148-018-0563-3","article-title":"The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes","volume":"10","author":"Alvarez","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.bmc.2014.02.018","article-title":"Studies on the antiproliferative effects of tropolone derivatives in Jurkat T-lymphocyte cells","volume":"22","author":"Ononye","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/j.bcp.2013.03.006","article-title":"Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies","volume":"85","author":"Shanmugam","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1021\/acs.molpharmaceut.7b00469","article-title":"Pharmacokinetics and Pharmacodynamics of the Triterpenoid Ursolic Acid in Regulating the Antioxidant, Anti-Inflammatory, and Epigenetic Gene Responses in Rat Leukocytes","volume":"14","author":"Zhang","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1080\/14786419.2018.1455043","article-title":"Macrocyclic bis-quinolizidine alkaloids from Xestospongia muta","volume":"33","author":"Dung","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1039\/C4FO00423J","article-title":"Antrodia camphorata induces G 1 cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice","volume":"5","author":"Yang","year":"2014","journal-title":"Food Funct."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1207\/s15327914nc4802_9","article-title":"Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cells","volume":"48","author":"Hseu","year":"2004","journal-title":"Nutr. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/j.biocel.2007.05.010","article-title":"Feijoa sellowiana derived natural Flavone exerts anti-cancer action displaying HDAC inhibitory activities","volume":"39","author":"Bontempo","year":"2007","journal-title":"Int. J. Biochem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1021\/jf3011239","article-title":"Comparison of Phenolic Acids Profile and Antioxidant Potential of Six Varieties of Spelt (Triticum spelta L.)","volume":"60","author":"Dziki","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/jn\/138.8.1411","article-title":"Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells","volume":"138","author":"Fabiani","year":"2008","journal-title":"J. Nutr."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2808\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:37:15Z","timestamp":1760125035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":138,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cancers15102808"],"URL":"https:\/\/doi.org\/10.3390\/cancers15102808","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}