{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:46:16Z","timestamp":1782369976029,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lavandula dentata is a medicinal and aromatic plant rich in specialised secondary metabolites, but the biomedical potential of leaf-surface metabolites recovered from pruning biomass remains poorly investigated. In this study, a pruning-derived leaf-surface extract of L. dentata was obtained by brief acetone immersion followed by n-hexane partitioning. Its chemical profile was investigated by ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry analysis combined with feature-based molecular networking, which revealed an enrichment in methoxylated flavonoids and pentacyclic triterpenes, including oleanane- and ursane-like derivatives. The biological activity of the extract was evaluated in HCT116 colorectal cancer cells, MDA-MB-231 triple-negative breast cancer cells, and HaCaT keratinocytes. After 24 h treatment, the extract selectively reduced HCT116 cell viability in a concentration-dependent manner, with an IC50 of 27.8 \u00b1 1.049 \u03bcg\/mL, whereas MDA-MB-231 and HaCaT cells were less sensitive. Mechanistic analyses in HCT116 cells showed increased early and late apoptotic populations, mitochondrial membrane depolarisation, and enhanced cleavage of caspase-9, caspase-3, and PARP. These findings indicate that a chemically profiled L. dentata leaf-surface extract selectively impairs colorectal cancer cell survival by activating mitochondria-mediated apoptosis. The study also supports the valorisation of pruning-derived aromatic plant biomass as a source of bioactive natural products with potential biomedical relevance.<\/jats:p>","DOI":"10.3390\/ijms27125535","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Profiling and Selective Pro-Apoptotic Activity of a Pruning-Derived Lavandula dentata Leaf-Surface Extract in Colorectal Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Shiva Pouramin","family":"Arabi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Scivicco","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0959-8982","authenticated-orcid":false,"given":"Valentina","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-4156","authenticated-orcid":false,"given":"Nunziatina","family":"De Tommasi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"},{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitale","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-9844","authenticated-orcid":false,"given":"Nunzio Antonio","family":"Cacciola","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorella","family":"Severino","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"176013","DOI":"10.1016\/j.ejphar.2023.176013","article-title":"Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery","volume":"958","author":"Davodabadi","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Garg, P., Malhotra, J., Kulkarni, P., Horne, D., Salgia, R., and Singhal, S.S. (2024). Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells. Cancers, 16.","DOI":"10.3390\/cancers16132478"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1039\/D4RA05089D","article-title":"Incredible use of plant-derived bioactives as anticancer agents","volume":"15","author":"Kangra","year":"2025","journal-title":"RSC Adv."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ma, J., Wang, X., and Sun, Q. (2026). Beyond cytotoxicity: Molecular mechanisms of natural products as multi-targeting modulators and chemo-sensitizers in oncology. Front. Pharmacol., 17.","DOI":"10.3389\/fphar.2026.1782874"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00210-023-02392-x","article-title":"A review of the bioactive components and pharmacological properties of Lavandula species","volume":"396","author":"Batiha","year":"2023","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dobros, N., Zawada, K.D., and Paradowska, K. (2022). Phytochemical Profiling, Antioxidant and Anti-Inflammatory Activity of Plants Belonging to the Lavandula Genus. Molecules, 28.","DOI":"10.3390\/molecules28010256"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Haban, M., Korczyk-Szabo, J., Certekova, S., and Razna, K. (2023). Lavandula Species, Their Bioactive Phytochemicals, and Their Biosynthetic Regulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108831"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.sajb.2023.01.023","article-title":"Traditional use, phytochemistry, toxicology, and pharmacological properties of Lavandula dentata L.: A comprehensive review","volume":"154","author":"Bouyahya","year":"2023","journal-title":"S. Afr. J. Bot."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8540","DOI":"10.1038\/s41598-025-88824-5","article-title":"Lavandula dentata leaves as potential natural antibiofilm agents against Pseudomonas aeruginosa","volume":"15","author":"Aboulwafa","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jep.2016.05.063","article-title":"Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.","volume":"190","author":"Algieri","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"El Abdali, Y., Agour, A., Allali, A., Bourhia, M., El Moussaoui, A., Eloutassi, N., Salamatullah, A.M., Alzahrani, A., Ouahmane, L., and Aboul-Soud, M.A.M. (2022). Lavandula dentata L.: Phytochemical Analysis, Antioxidant, Antifungal and Insecticidal Activities of Its Essential Oil. Plants, 11.","DOI":"10.3390\/plants11030311"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1080\/01480545.2022.2104868","article-title":"Phytochemical composition, cytotoxicity, antioxidant and antimicrobial responses of Lavandula dentata L. grown under different levels of heavy metals stress condition","volume":"46","author":"Terfi","year":"2023","journal-title":"Drug Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/elps.201700393","article-title":"Phytochemical profiling of anti-inflammatory Lavandula extracts via RP-HPLC-DAD-QTOF-MS and -MS\/MS: Assessment of their qualitative and quantitative differences","volume":"39","author":"Contreras","year":"2018","journal-title":"Electrophoresis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2000532","DOI":"10.1002\/cbdv.202000532","article-title":"Lavandula dentata from Italy: Analysis of Trichomes and Volatiles","volume":"17","author":"Giuliani","year":"2020","journal-title":"Chem. Biodivers."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1080\/15287394.2025.2549913","article-title":"Bioactive compounds and cytotoxic activity of Lavandula dentata extract obtained via supercritical extraction","volume":"89","author":"Lima","year":"2026","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.4238\/2014.May.23.9","article-title":"In vitro cytotoxicity screening of wild plant extracts from Saudi Arabia on human breast adenocarcinoma cells","volume":"13","author":"Ali","year":"2014","journal-title":"Genet. Mol. Res."},{"key":"ref_21","first-page":"757","article-title":"Specific induction of apoptosis by 1,8-cineole in two human leukemia cell lines, but not a in human stomach cancer cell line","volume":"9","author":"Moteki","year":"2002","journal-title":"Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.3892\/or.2013.2763","article-title":"Antitumor effect of 1, 8-cineole against colon cancer","volume":"30","author":"Murata","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pyo, Y., Kwon, K.H., and Jung, Y.J. (2024). Anticancer Potential of Flavonoids: Their Role in Cancer Prevention and Health Benefits. Foods, 13.","DOI":"10.3390\/foods13142253"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.biopha.2017.06.056","article-title":"Evaluation of in vitro anticancer activity of 1,8-Cineole-containing n-hexane extract of Callistemon citrinus (Curtis) Skeels plant and its apoptotic potential","volume":"93","author":"Sampath","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/01635581.2013.878736","article-title":"Comparative studies of cytotoxic and apoptotic properties of different extracts and the essential oil of Lavandula angustifolia on malignant and normal cells","volume":"66","author":"Amiri","year":"2014","journal-title":"Nutr. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mahmoud, S.S., Maddock, S., and Adal, A.M. (2021). Isoprenoid Metabolism and Engineering in Glandular Trichomes of Lamiaceae. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.699157"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Crisan, I., Ona, A., Varban, D., Muntean, L., Varban, R., Stoie, A., Mihaiescu, T., and Morea, A. (2023). Current Trends for Lavender (Lavandula angustifolia Mill.) Crops and Products with Emphasis on Essential Oil Quality. Plants, 12.","DOI":"10.3390\/plants12020357"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20922","DOI":"10.1038\/s41598-024-71115-w","article-title":"Evaluation of lavender essential oils and by-products using microwave hydrodistillation and conventional hydrodistillation","volume":"14","author":"Kirkinci","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_29","first-page":"145","article-title":"Resource-Efficient Use of Residues from Medicinal and Aromatic Plants for Production of Secondary Plant Metabolites","volume":"188","author":"Kummritz","year":"2024","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e9243","DOI":"10.1002\/rcm.9243","article-title":"Structure-fragmentation study of pentacyclic triterpenoids using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOFMS\/MS)","volume":"36","author":"Uddin","year":"2022","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113310","DOI":"10.1016\/j.phytochem.2022.113310","article-title":"Cytotoxic abietane diterpenoids from Salvia leriifolia Benth","volume":"202","author":"Sarhadi","year":"2022","journal-title":"Phytochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110010","DOI":"10.1016\/j.cbi.2022.110010","article-title":"Oleanolic acid induces HCT116 colon cancer cell death through the p38\/FOXO3a\/Sirt6 pathway","volume":"363","author":"Potocnjak","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lin, C.M., Chao, M.C., Chen, H.H., and Chen, H.J. (2025). Ursolic Acid Suppresses Colorectal Cancer Through Autophagy-Lysosomal Degradation of beta-Catenin. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136210"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s43440-024-00684-4","article-title":"Ursolic acid in colorectal cancer: Mechanisms, current status, challenges, and future research directions","volume":"77","author":"Zhang","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"AlMousa, L.A., Pandey, P., Lakhanpal, S., Kyada, A.K., H, M., Nayak, P.P., Hussain, A., Hasan, T.N., Alagal, R.I., and Khan, F. (2025). An updated review deciphering the anticancer potential of pentacyclic triterpene lupeol and its nanoformulations. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1594901"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.jaim.2025.101270","article-title":"Signaling pathways and molecular mechanisms of lupeol in colorectal cancer: A comprehensive review","volume":"17","author":"Farooqi","year":"2026","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sevim Nalkiran, H., and Nalkiran, I. (2025). Anticancer Effects and Phytochemical Profile of Lavandula stoechas. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111706"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1073\/pnas.0813333106","article-title":"A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53","volume":"106","author":"Sur","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1186\/s12967-025-06566-4","article-title":"p53 in colorectal cancer: From a master player to a privileged therapy target","volume":"23","author":"Yan","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hassan, A., and Aubel, C. (2025). The PI3K\/Akt\/mTOR Signaling Pathway in Triple-Negative Breast Cancer: A Resistance Pathway and a Prime Target for Targeted Therapies. Cancers, 17.","DOI":"10.3390\/cancers17132232"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"60712","DOI":"10.18632\/oncotarget.10858","article-title":"Triple negative breast cancer: Shedding light onto the role of pi3k\/akt\/mtor pathway","volume":"7","author":"Massihnia","year":"2016","journal-title":"Oncotarget"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wu, T.N., Chen, H.M., and Shyur, L.F. (2021). Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413571"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Grabowska, K., Galanty, A., Pecio, L., Stojakowska, A., Malarz, J., Zmudzki, P., Zagrodzki, P., and Podolak, I. (2024). Selectivity Screening and Structure-Cytotoxic Activity Observations of Selected Oleanolic Acid (OA)-Type Saponins from the Amaranthaceae Family on a Wiade Panel of Human Cancer Cell Lines. Molecules, 29.","DOI":"10.3390\/molecules29163794"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1038\/s41598-025-30998-z","article-title":"In vitro anticancer studies of new derivatives based on the furanocoumarin scaffold","volume":"16","author":"Olejarz","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yazir, M., Bayar Muluk, N., Alaskarov, E., Bulbul, M.V., Acar, T.Y., Keskin, I., and Cingi, C. (2025). Anticancer Effects of Lavandula Angustifolia, L. Essential Oil: Dose-Dependent Cytotoxicity in HNO210 Human Laryngeal Carcinoma Cells. J. Craniofacial Surg.","DOI":"10.1097\/SCS.0000000000012293"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2478\/acph-2025-0034","article-title":"Anticancer activity of Lavandula stoechas L. flower ethanolic extract through apoptotic pathway modulation in colorectal cancer cells","volume":"75","author":"Dogru","year":"2025","journal-title":"Acta Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ovidi, E., Masci, V.L., Taddei, A.R., Paolicelli, P., Petralito, S., Trilli, J., Mastrogiovanni, F., Tiezzi, A., Casadei, M.A., and Giacomello, P. (2020). Chemical Investigation and Screening of Anti-Proliferative Activity on Human Cell Lines of Pure and Nano-Formulated Lavandin Essential Oil. Pharmaceuticals, 13.","DOI":"10.3390\/ph13110352"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/cyto.10028","article-title":"The dynamic process of apoptosis analyzed by flow cytometry using Annexin-V\/propidium iodide and a modified in situ end labeling technique","volume":"47","author":"Span","year":"2002","journal-title":"Cytometry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/cyto.a.20889","article-title":"Cytometry in cell necrobiology revisited. Recent advances and new vistas","volume":"77","author":"Wlodkowic","year":"2010","journal-title":"Cytom. A"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Brentnall, M., Rodriguez-Menocal, L., De Guevara, R.L., Cepero, E., and Boise, L.H. (2013). Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol., 14.","DOI":"10.1186\/1471-2121-14-32"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1091\/mbc.e06-04-0263","article-title":"Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization","volume":"18","author":"Samraj","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e3128","DOI":"10.21769\/BioProtoc.3128","article-title":"Analysis of the Mitochondrial Membrane Potential Using the Cationic JC-1 Dye as a Sensitive Fluorescent Probe","volume":"9","author":"Sivandzade","year":"2019","journal-title":"Bio Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115473","DOI":"10.1016\/j.biopha.2023.115473","article-title":"Natural products and mitochondrial allies in colorectal cancer therapy","volume":"167","author":"Wei","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Laghezza Masci, V., Ovidi, E., Taddei, A.R., Turchetti, G., Tiezzi, A., Giacomello, P., and Garzoli, S. (2020). Apoptotic Effects on HL60 Human Leukaemia Cells Induced by Lavandin Essential Oil Treatment. Molecules, 25.","DOI":"10.3390\/molecules25030538"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3892\/mmr.2022.12898","article-title":"Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway","volume":"27","author":"Hu","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13612","DOI":"10.1039\/D5RA09216G","article-title":"Context-dependent cytotoxicity and ADMET profiling of methoxylated flavonoids as novel leads for metastatic prostate cancer","volume":"16","author":"Hourani","year":"2026","journal-title":"RSC Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"108343","DOI":"10.1016\/j.bioorg.2025.108343","article-title":"Semi-synthetic flavonoid derivatives from Boesenbergiarotunda induce extrinsic apoptosis pathway via Caspase-3 and Caspase-8 in HCT116 Colon Cancer cell lines","volume":"159","author":"Janthong","year":"2025","journal-title":"Bioorganic Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hikisz, P., Adamus-Grabicka, A.A., and Budzisz, E. (2026). Multifaceted Anticancer Activity of Flavanone\/Chromanone Intermediates for Five-Membered Heterocyclic Derivatives: Targeting Oxidative Stress, Apoptosis, and MAPK Signaling in Colorectal Cancer. Molecules, 31.","DOI":"10.3390\/molecules31030534"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Perez-Magarino, S., Bueno-Herrera, M., and Asensio, S.M.M.C. (2024). Characterization of Bioactive Phenolic Compounds Extracted from Hydro-Distillation By-Products of Spanish Lamiaceae Plants. Molecules, 29.","DOI":"10.3390\/molecules29225285"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/bmc.1614","article-title":"Identification and quantification of oleanolic acid and ursolic acid in Chinese herbs by liquid chromatography-ion trap mass spectrometry","volume":"25","author":"Chen","year":"2011","journal-title":"Biomed. Chromatogr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/jms.1472","article-title":"Analysis of pentacyclic triterpenes by LC-MS. A comparative study between APCI and APPI","volume":"44","author":"Chaimbault","year":"2009","journal-title":"J. Mass Spectrom."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Parisi, V., Donadio, G., Bellone, M.L., Belaabed, S., Bader, A., Bisio, A., Iobbi, V., Gazzillo, E., Chini, M.G., and Bifulco, G. (2023). Exploring the Anticancer Potential of Premna resinosa (Hochst.) Leaf Surface Extract: Discovering New Diterpenes as Heat Shock Protein 70 (Hsp70) Binding Agents. Plants, 12.","DOI":"10.3390\/plants12132421"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41587-023-01690-2","article-title":"Integrative analysis of multimodal mass spectrometry data in MZmine 3","volume":"41","author":"Schmid","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"114906","DOI":"10.1016\/j.phytochem.2026.114906","article-title":"Diterpenes from Hypoestes forskaolii leaves and their cytotoxic activity","volume":"248","author":"Parisi","year":"2026","journal-title":"Phytochemistry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41596-025-01237-6","article-title":"A versatile toolkit for drug metabolism studies with GNPS2: From drug development to clinical monitoring","volume":"21","author":"Yu","year":"2026","journal-title":"Nat. Protoc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"pdb prot087379","DOI":"10.1101\/pdb.prot087379","article-title":"Crystal Violet Assay for Determining Viability of Cultured Cells","volume":"2016","author":"Feoktistova","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12964-023-01271-5","article-title":"Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis","volume":"21","author":"Cacciola","year":"2023","journal-title":"Cell Commun. 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