{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:04Z","timestamp":1787029324681,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011665","name":"Deanship of Scientific Research, King Saud University","doi-asserted-by":"publisher","award":["Vice Deanship of Research Chairs"],"award-info":[{"award-number":["Vice Deanship of Research Chairs"]}],"id":[{"id":"10.13039\/501100011665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive\u2122 HF Hybrid Quadrupole-Orbitrap\u2122 coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC\/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.<\/jats:p>","DOI":"10.3390\/plants9101295","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T09:04:12Z","timestamp":1601543052000},"page":"1295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Biochemical and Molecular Investigation of In Vitro Antioxidant and Anticancer Activity Spectrum of Crude Extracts of Willow Leaves Salix safsaf"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-0563","authenticated-orcid":false,"given":"Mourad A. M.","family":"Aboul-Soud","sequence":"first","affiliation":[{"name":"Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelkader E.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Kulliyyah (College) of Medicine, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan K.","family":"Challis","sequence":"additional","affiliation":[{"name":"Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-8428","authenticated-orcid":false,"given":"Atallah F.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Nassrallah","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Agriculture, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-3031","authenticated-orcid":false,"given":"Tariq A.","family":"Alahmari","sequence":"additional","affiliation":[{"name":"Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quaiser","family":"Saquib","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maqsood A.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazeed","family":"Al-Sheikh","sequence":"additional","affiliation":[{"name":"Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany A.","family":"El-Shemy","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Agriculture, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-3451","authenticated-orcid":false,"given":"Ahmed M.","family":"Aboul-Enein","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Agriculture, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Dermatology, College of Medicine, P.O. Box 240997, King Saud University, Riyadh 11322, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada"},{"name":"School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Giesy","sequence":"additional","affiliation":[{"name":"Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada"},{"name":"Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada"},{"name":"Department of Environmental Science, Baylor University, Waco, TX 76798-7266 (254), USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"390","author":"Naghavi","year":"2017","journal-title":"Lancet"},{"key":"ref_2","unstructured":"American Cancer Society (2020, July 11). Cancer Facts & Figures 2019. Available online: https:\/\/www.cancer.org\/...\/2019\/cancer-facts-and-figures-2019.pdf."},{"key":"ref_3","unstructured":"Stewart, B.W., and Wild, C.P. (2014). World Cancer Report 2014, International Agency for Research on Cancer, WHO Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural Products as Sources of New Drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1039\/C4NP00064A","article-title":"Natural product and natural product derived drugs in clinical trials","volume":"31","author":"Butler","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mussarat, S., Abdel-Salam, N.M., Tariq, A., Wazir, S.M., Ullah, R., and Adnan, M. (2014). Use of Ethnomedicinal Plants by the People Living around Indus River. Evid. Based Complement. Altern. Med., 2014.","DOI":"10.1155\/2014\/212634"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/ptr.5751","article-title":"A systematic review on ethnomedicines of anti-cancer plants","volume":"31","author":"Tariq","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s10495-015-1169-2","article-title":"Cell death mechanisms of plant-derived anticancer drugs: Beyond apoptosis","volume":"20","author":"Hmadi","year":"2015","journal-title":"Apoptosis"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hassan, B. (2020). Plants and Cancer Treatment. Med. Plants Use Prev. Treat. Dis. IntechOpen.","DOI":"10.5772\/intechopen.90568"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1016\/j.ejmech.2011.07.057","article-title":"Natural products: An evolving role in future drug discovery","volume":"46","author":"Mishra","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"517S","DOI":"10.1093\/ajcn\/78.3.517S","article-title":"Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals","volume":"78","author":"Liu","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3479S","DOI":"10.1093\/jn\/134.12.3479S","article-title":"Potential synergy of phytochemicals in cancer prevention: Mechanism of action","volume":"134","author":"Liu","year":"2004","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1365-2184.2006.00377.x","article-title":"The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential","volume":"39","author":"Mahdi","year":"2006","journal-title":"Cell Prolif."},{"key":"ref_14","first-page":"387","article-title":"The effect of willow leaf extracts on human leukemic cells in vitro","volume":"36","author":"Issa","year":"2003","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"El-Shemy, H.A., Aboul-Enein, A.M., Aboul-Enein, K.M., and Fujita, K. (2007). Willow Leaves\u2019 Extracts Contain Anti-Tumor Agents Effective against Three Cell Types. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000178"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Aboul-Soud, M.A., Al-Amri, M.Z., Kumar, A., Al-Sheikh, Y., Ashour, A.E., and El-Kersh, T.A. (2019). Specific Cytotoxic Effects of Parasporal Crystal Proteins Isolated from Native Saudi Arabian Bacillus thuringiensis Strains against Cervical Cancer Cells. Molecules, 24.","DOI":"10.3390\/molecules24030506"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11010-016-2703-4","article-title":"Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-\u03baB signaling and IL-8 expression","volume":"416","author":"Ashour","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6658","DOI":"10.1021\/jm049486a","article-title":"Discovery ofN-(2-Chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a Dual Src\/Abl Kinase Inhibitor with Potent Antitumor Activity in Preclinical Assays","volume":"47","author":"Lombardo","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_19","first-page":"1","article-title":"Crude Methanol Extract of Rosin Gum Exhibits Specific Cytotoxicity against Human Breast Cancer Cells via Apoptosis Induction","volume":"20","author":"Soliman","year":"2020","journal-title":"AntiCancer Agents Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.mrgentox.2012.01.001","article-title":"Cytotoxic and necrotic responses in human amniotic epithelial (WISH) cells exposed to organophosphate insecticide phorate","volume":"744","author":"Saquib","year":"2012","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.taap.2011.12.006","article-title":"Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats","volume":"259","author":"Saquib","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Seca, A.M.L., and Pinto, D.C.G.A. (2018). Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010263"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Solowey, E., Lichtenstein, M., Sallon, S., Paavilainen, H., Solowey, E., and Lorberboum-Galski, H. (2014). Evaluating Medicinal Plants for Anticancer Activity. Sci. World J., 2014.","DOI":"10.1155\/2014\/721402"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.drudis.2007.10.010","article-title":"Plant-derived compounds in clinical trials","volume":"13","author":"Saklani","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3892\/ol.2015.3916","article-title":"Effects of plant-derived anti-leukemic drugs on individualized leukemic cell population profiles in Egyptian patients","volume":"11","author":"Mahmoud","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2174\/092986710790112620","article-title":"Antitumor Properties and Modulation of Antioxidant Enzymes Activity by Aloe vera Leaf Active Principles Isolated via Supercritical Carbon Dioxide Extraction","volume":"17","author":"Kabash","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.3892\/ijo.2016.3418","article-title":"Transcriptional profiling of breast cancer cells in response to mevinolin: Evidence of cell cycle arrest, DNA degradation and apoptosis","volume":"48","author":"Mahmoud","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_28","first-page":"635","article-title":"Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats","volume":"21","author":"Habila","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3892\/etm.2017.4522","article-title":"Ascorbate ameliorates Echis coloratus venom-induced oxidative stress in human fibroblasts","volume":"14","author":"Ghneim","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_30","first-page":"799","article-title":"Anti-cancer and anti-oxidant activity of some Egyptian medicinal plants","volume":"3","author":"Lightfoot","year":"2009","journal-title":"J. Med. Plants Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1080\/01635581.2013.850966","article-title":"Anticarcinogenic Effects of the Ethanolic Extract ofSalix aegyptiacain Colon Cancer Cells: Involvement of Akt\/PKB and MAPK Pathways","volume":"65","author":"Enayat","year":"2013","journal-title":"Nutr. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.trac.2019.01.002","article-title":"Recent applications of high resolution mass spectrometry for the characterization of plant natural products","volume":"112","author":"Cifuentes","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.chroma.2016.02.079","article-title":"A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering","volume":"1441","author":"Qiao","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2174\/1389202917666160808125645","article-title":"Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies","volume":"18","author":"Orellana","year":"2017","journal-title":"Curr. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4103\/0973-1296.131023","article-title":"The extracts of Japanese willow tree species are effective forapoptotic desperation or differentiation of acute myeloid leukemia cells","volume":"10","author":"Fujita","year":"2014","journal-title":"Pharmacogn. Mag."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1104\/pp.124.2.767","article-title":"Effects of Elevated [CO2] and Nitrogen Nutrition on Cytokinins in the Xylem Sap and Leaves of Cotton","volume":"124","author":"Yong","year":"2000","journal-title":"Plant Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/jxb\/erm157","article-title":"Regulation of cytokinin biosynthesis, compartmentalization and translocation","volume":"59","author":"Hirose","year":"2008","journal-title":"J. Exp. Bot."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1365-2141.2005.05907.x","article-title":"Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0\/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells","volume":"132","author":"Bacher","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Abo-Salem, H.M., Nassrallah, A., Soliman, A.A., Ebied, M.S., Elawady, M.E., Abdelhamid, S.A., El-Sawy, E.R., Al-Sheikh, Y., and Aboul-Soud, M.A. (2020). Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects. Molecules, 25.","DOI":"10.3390\/molecules25051124"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11903","DOI":"10.1007\/s13277-014-2457-0","article-title":"Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8\/-9\/-3 signals in human acute myeloid leukemia cells","volume":"35","author":"Hsiao","year":"2014","journal-title":"Tumor Boil."},{"key":"ref_41","first-page":"1269","article-title":"Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: O-coumaric acid\u2014PubMed","volume":"8","author":"Atmaca","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/13880209.2013.781194","article-title":"Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells","volume":"51","author":"Abaza","year":"2013","journal-title":"Pharm. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1177\/0960327119839173","article-title":"Syringic acid triggers reactive oxygen species-mediated cytotoxicity in HepG2 cells","volume":"38","author":"Gheena","year":"2019","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sheikh, M.S., and Fornace, A.J. (2000). Role of p53 family members in apoptosis. J. Cell. Physiol., 182.","DOI":"10.1002\/(SICI)1097-4652(200002)182:2<171::AID-JCP5>3.0.CO;2-3"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.04-2226fje","article-title":"Ablation of either p21 or Bax prevents p53-dependent apoptosis induced by green tea polyphenol epigallocatechin-3-gallate","volume":"19","author":"Hastak","year":"2005","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11598","DOI":"10.1073\/pnas.181181198","article-title":"A phosphatidylinositol 3-kinase\/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus","volume":"98","author":"Mayo","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1002\/ptr.3386","article-title":"Willow Species and Aspirin: Different Mechanism of Actions","volume":"25","author":"Vlachojannis","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00210-017-1407-y","article-title":"Anticancer activity of salicin and fenofibrate","volume":"390","author":"Sabaa","year":"2017","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hamadou, M.H., Kerkatou, M., Gatto, P., Pancher, M., Bisio, A., Inga, A., Menad, A., Benayache, S., Benayache, F., and Ameddah, S. (2019). Apigenin rich-Limonium duriusculum (de Girard) Kuntze promotes apoptosis in HCT116 cancer cells. Nat. Prod. Res.","DOI":"10.1080\/14786419.2019.1672070"},{"key":"ref_50","first-page":"1661","article-title":"Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer","volume":"52","author":"Maeda","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4566","DOI":"10.3892\/mmr.2015.3906","article-title":"Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5\u2032-adenosine monophosphate-activated protein kinase activation","volume":"12","author":"Hsu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9473","DOI":"10.2147\/OTT.S216620","article-title":"Effects of Adenosine on Apoptosis of Ovarian Cancer A2780 Cells via ROS and Caspase Pathways","volume":"12","author":"Xia","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"678","DOI":"10.7150\/ijms.42086","article-title":"Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade","volume":"17","author":"Su","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_54","first-page":"19","article-title":"Control of differentiation and apoptosis of human myeloid leukemia cells by cytokinins and cytokinin nucleosides, plant redifferentiation-inducing hormones","volume":"13","author":"Ishii","year":"2002","journal-title":"Cell Growth Differ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109","DOI":"10.18388\/pb.2019_265","article-title":"Biological activity of N6-furfuryladenosine","volume":"65","author":"Wawrzyniak","year":"2019","journal-title":"Post\u0119py Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.phrs.2010.06.004","article-title":"Cytoprotective effects of olive mill wastewater extract and its main constituent hydroxytyrosol in PC12 cells","volume":"62","author":"Schaffer","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_57","first-page":"91","article-title":"Molecular basis of the anti-cancer effects of genistein isoflavone in LNCaP prostate cancer cells","volume":"1","author":"Merchant","year":"2011","journal-title":"Funct. Foods Heal. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lee, J., Park, A., Son, H., Lim, H.-J., Rha, Y.-A., and Kang, H. (2017). Spirulina Extract Enhanced a Protective Effect in Type 1 Diabetes by Anti-Apoptosis and Anti-ROS Production. Nutrients, 9.","DOI":"10.3390\/nu9121363"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ferhi, S., Santaniello, S., Zerizer, S., Cruciani, S., Fadda, A., Sanna, D., Dore, A., Maioli, M., and D\u2019Hallewin, G. (2019). Total Phenols from Grape Leaves Counteract Cell Proliferation and Modulate Apoptosis-Related Gene Expression in MCF-7 and HepG2 Human Cancer Cell Lines. Molecules, 24.","DOI":"10.3390\/molecules24030612"},{"key":"ref_60","first-page":"459","article-title":"Some current insights into oxidative stress","volume":"8408","year":"2010","journal-title":"Physiol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Abramovi\u010d, H. (2015). Antioxidant Properties of Hydroxycinnamic Acid Derivatives. Coffee Health Dis. Prev., 843\u2013852.","DOI":"10.1016\/B978-0-12-409517-5.00093-0"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1080\/21691401.2019.1629949","article-title":"Salicin prevents TNF-\u03b1-induced cellular senescence in human umbilical vein endothelial cells (HUVECs)","volume":"47","author":"Guo","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/10\/1295\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:23Z","timestamp":1760177723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/10\/1295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":62,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["plants9101295"],"URL":"https:\/\/doi.org\/10.3390\/plants9101295","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}