{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:18Z","timestamp":1788930498606,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006989","name":"Jackson State University","doi-asserted-by":"publisher","award":["5U4MD015929-04"],"award-info":[{"award-number":["5U4MD015929-04"]}],"id":[{"id":"10.13039\/100006989","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006989","name":"Jackson State University","doi-asserted-by":"publisher","award":["1R16GM153544-01A1"],"award-info":[{"award-number":["1R16GM153544-01A1"]}],"id":[{"id":"10.13039\/100006989","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5U4MD015929-04"],"award-info":[{"award-number":["5U4MD015929-04"]}],"id":[{"id":"https:\/\/ror.org\/01ecnnp60","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R16GM153544-01A1"],"award-info":[{"award-number":["1R16GM153544-01A1"]}],"id":[{"id":"https:\/\/ror.org\/01ecnnp60","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010065","name":"Morgan State University","doi-asserted-by":"publisher","award":["U54MD013376-06"],"award-info":[{"award-number":["U54MD013376-06"]}],"id":[{"id":"10.13039\/100010065","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U54MD013376-06"],"award-info":[{"award-number":["U54MD013376-06"]}],"id":[{"id":"https:\/\/ror.org\/017d8gk22","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016743","name":"Florida Agricultural and Mechanical University","doi-asserted-by":"publisher","award":["2417643"],"award-info":[{"award-number":["2417643"]}],"id":[{"id":"10.13039\/100016743","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2417643"],"award-info":[{"award-number":["2417643"]}],"id":[{"id":"https:\/\/ror.org\/00c4wc133","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Vernonia calvoana (VC), a commonly used medicinal plant in West Africa, has been shown by our research team to inhibit the proliferation of OVCAR-3 ovarian cancer cells through mechanisms involving oxidative stress, DNA damage, and S-phase cell cycle arrest. The objective of the current study was to elucidate the intrinsic apoptotic mechanisms triggered by VC fraction seven (VCF7). OVCAR-3 cells were treated with VCF7 (0, 8, 16, and 32 \u03bcg\/mL) for a duration of 48 h. Apoptosis was assessed using Annexin V\/Propidium Iodide (PI) staining followed by flow cytometry analysis. Mitochondrial membrane potential (\u0394\u03a8m) was assessed through JC-1 staining and confocal microscopy, while chromatin condensation was analyzed using DAPI staining. DNA fragmentation was examined by agarose gel electrophoresis. Caspase 3 activity was measured using flow cytometry. Protein expression levels of p53, Bcl-2, cytochrome c, caspase-9, and caspase-3 were determined by Western blot analysis, and mRNA expression levels of p53 and Bcl-2 were evaluated using qRT-PCR. VCF7 induced apoptosis in a concentration-dependent manner. Analysis using Annexin V\/PI indicated an increase in apoptotic cell populations from 10.5% to 30%, along with a rise in necrotic cells from 7% to 50% across treatment concentrations. A modest, concentration-associated decrease in mitochondrial membrane potential was recorded (0.96-, 0.88-, and 0.85-fold at 8, 16, and 32 \u03bcg\/mL, respectively; p &lt; 0.05). DAPI staining validated the concentration-dependent chromatin condensation and nuclear fragmentation. The analysis of DNA fragmentation showed progressive internucleosomal degradation, appearing as a smear pattern with distinct fragments at elevated concentrations, indicative of concurrent apoptotic and necrotic cell death. The activation of caspase-3 reached a peak of 28% at 16 \u03bcg\/mL. Western blot analysis indicated an upregulation of p53, a downregulation of Bcl-2, an increase in total cytochrome c protein levels, and an increased expression of caspase-9 and caspase-3 in a concentration-dependent manner. These findings were corroborated at the transcriptional level by qRT-PCR, which showed increased p53 mRNA and decreased Bcl-2 mRNA expression. Taken together, these results underscore the potential of VCF7 as a promising plant-derived anticancer agent and support the need for further preclinical and clinical studies in ovarian cancer.<\/jats:p>","DOI":"10.3390\/ijms27177887","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:13:25Z","timestamp":1788455605000},"page":"7887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights into Vernonia calvoana-Induced Apoptosis in Ovarian Cancer Cells via the Intrinsic Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Ariane M.","family":"Chitoh","sequence":"first","affiliation":[{"name":"Research Center for Health Disparities Research and Innovation (RCMI), Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"},{"name":"Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-0720","authenticated-orcid":false,"given":"Clement G.","family":"Yedjou","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid K.","family":"Tchakoua","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvianne","family":"Njiki","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3192-5132","authenticated-orcid":false,"given":"Felicite K.","family":"Noubissi","sequence":"additional","affiliation":[{"name":"Research Center for Health Disparities Research and Innovation (RCMI), Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"},{"name":"Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titilope","family":"Komolafe","sequence":"additional","affiliation":[{"name":"Research Center for Health Disparities Research and Innovation (RCMI), Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-5863","authenticated-orcid":false,"given":"Kayode","family":"Komolafe","sequence":"additional","affiliation":[{"name":"Research Center for Health Disparities Research and Innovation (RCMI), Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatoyin V.","family":"Odubanjo","sequence":"additional","affiliation":[{"name":"Research Center for Health Disparities Research and Innovation (RCMI), Jackson State University, 1400 Lynch Street, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2178-2699","authenticated-orcid":false,"given":"Paul B.","family":"Tchounwou","sequence":"additional","affiliation":[{"name":"Research Center for Urban Health Disparities Research and Innovation (RCMI), Morgan State University, 1700 E. Cold Spring Lane, Baltimore, MD 21251, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41571-024-00881-3","article-title":"Global epidemiology of epithelial ovarian cancer","volume":"21","author":"Webb","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2400313","DOI":"10.1200\/GO-24-00313","article-title":"Socioeconomic Burden of Ovarian Cancer in 11 Countries","volume":"11","author":"Hutchinson","year":"2025","journal-title":"JCO Glob. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, Y., Song, W., Gao, P., Guan, X., Wang, B., Zhang, L., Yao, Y., Guo, Y., Wang, Y., and Jiang, S. (2025). Global, regional, and national burden of breast, cervical, uterine, and ovarian cancer and their risk factors among women from 1990 to 2021, and projections to 2050: Findings from the global burden of disease study 2021. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13741-9"},{"key":"ref_5","first-page":"284","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13048-017-0355-y","article-title":"Racial health disparities in ovarian cancer: Not just black and white","volume":"10","author":"Srivastava","year":"2017","journal-title":"J. Ovarian Res."},{"key":"ref_7","first-page":"1261","article-title":"The effect of time on racial differences in epithelial ovarian cancer (OVCA) diagnosis stage, overall and by histologic subtypes: A study of the National Cancer Database","volume":"27","author":"Peterson","year":"2016","journal-title":"Cancer Causes Control"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"pkz084","DOI":"10.1093\/jncics\/pkz084","article-title":"Race, socioeconomic status, and health-care access disparities in Ovarian cancer treatment and mortality: Systematic review and meta-analysis","volume":"3","author":"Karanth","year":"2019","journal-title":"JNCI Cancer Spectr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41416-023-02471-z","article-title":"Epithelial ovarian cancer survival by race and ethnicity in an equal-access healthcare population","volume":"130","author":"Arter","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.1158\/1078-0432.CCR-16-1119","article-title":"Racial\/ethnic disparities in ovarian cancer treatment and survival","volume":"22","author":"Bandera","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1097\/AOG.0b013e3182a92011","article-title":"Racial disparities in the treatment of advanced epithelial ovarian cancer","volume":"122","author":"Howell","year":"2013","journal-title":"Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13048-022-01020-1","article-title":"Maintenance therapy for newly diagnosed epithelial ovarian cancer\u2014A review","volume":"15","author":"Nag","year":"2022","journal-title":"J. Ovarian Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1517\/13543784.2010.515585","article-title":"Overcoming platinum resistance in ovarian carcinoma","volume":"19","author":"Matsuo","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, G., Yang, H., Wang, Y., and Qin, J. (2025). Ovarian cancer targeted therapy: Current landscape and future challenges. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1535235"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s11864-024-01190-8","article-title":"Ovarian Suppression: Early Menopause and Late Effects","volume":"25","author":"Molinelli","year":"2024","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_16","first-page":"4151","article-title":"Management of nephrotoxicity of chemotherapy and targeted agents: 2020","volume":"10","author":"Chiruvella","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123125","DOI":"10.1016\/j.lfs.2024.123125","article-title":"Bortezomib in cancer therapy: Mechanisms, side effects, and future proteasome inhibitors","volume":"358","author":"Sogbein","year":"2024","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ekor, M. (2014). The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Neurol., 4.","DOI":"10.3389\/fphar.2013.00177"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mazumder, K., Aktar, A., Roy, P., Biswas, B., Hossain, M.E., Sarkar, K.K., Bachar, S.C., Ahmed, F., Monjur-Al-Hossain, A.S.M., and Fukase, K. (2022). A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship. Molecules, 27.","DOI":"10.3390\/molecules27093036"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1016\/j.atherosclerosis.2016.07.557","article-title":"The impact of dietary supplementation of Vernonia calvoana leaves on serum lipid profile and haematological indices in albino wistar rats","volume":"252","author":"Egbung","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Eneji Egbung, G., Atangwho, J., Diana Odey, O., Victor Ndubuisi, A., and Ndiodimma, V.N. (2017). The Lipid Lowering and Cardioprotective Effects of Vernonia calvoana Ethanol Extract in Acetaminophen-Treated Rats. Medicines, 4.","DOI":"10.3390\/medicines4040090"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4314\/gjpas.v22i2.3","article-title":"Antioxidant activity of the inflorescents of Vernonia calvoana growing in Yakurr Local Government Area of Cross River State, Nigeria","volume":"22","author":"Egbung","year":"2016","journal-title":"Glob. J. Pure Appl. Sci."},{"key":"ref_23","first-page":"24","article-title":"Biochemical and antioxidants activity of crude, methanol and n-hexane fractions of Vernonia calvoana on streptozotocin induced diabetic rats","volume":"9","author":"Iwara","year":"2017","journal-title":"J. Pharmacogn. Phyther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"854","DOI":"10.5530\/pj.2018.5.144","article-title":"Analysis of bioactive constituents of n-hexane and methanol fractions of Vernonia calvoana extracts using gas chromatography-mass spectrometry","volume":"10","author":"Iwara","year":"2018","journal-title":"Pharmacogn. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mbemi, A.T., Sims, J.N., Yedjou, C.G., Noubissi, F.K., Gomez, C.R., and Tchounwou, P.B. (2020). Vernonia calvoana shows promise towards the treatment of ovarian cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124429"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0092-8674(00)00003-9","article-title":"Apoptotic pathways: Paper wraps stone blunts scissors","volume":"102","author":"Green","year":"2000","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"205","DOI":"10.15171\/apb.2019.024","article-title":"Understanding apoptosis and apoptotic pathways targeted cancer therapeutics","volume":"9","author":"Jan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrm1715","article-title":"Trashing the genome: The role of nucleases during apoptosis","volume":"6","author":"Samejima","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/cr.2016.159","article-title":"Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2","volume":"27","author":"Liang","year":"2016","journal-title":"Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41392-025-02176-0","article-title":"The BCL2 family: From apoptosis mechanisms to new advances in targeted therapy","volume":"10","author":"Vogler","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Matassov, D., Kagan, T., Leblanc, J., Sikorska, M., and Zakeri, Z. (2004). Measurement of apoptosis by DNA fragmentation. Apoptosis Methods and Protocols, Springer.","DOI":"10.1385\/1-59259-812-9:001"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev-biochem-060815-014710","article-title":"The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches","volume":"85","author":"Joerger","year":"2016","journal-title":"Annu Rev. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e288","DOI":"10.1002\/mco2.288","article-title":"Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies","volume":"4","author":"Shen","year":"2023","journal-title":"MedComm"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrc.2016.15","article-title":"The importance of p53 pathway genetics in inherited and somatic cancer genomes","volume":"16","author":"Stracquadanio","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6475624","DOI":"10.1155\/2016\/6475624","article-title":"Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies","volume":"2016","author":"Mileo","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.18632\/oncotarget.5754","article-title":"Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells","volume":"6","author":"Kumar","year":"2015","journal-title":"Oncotarget"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.molcel.2010.01.025","article-title":"The BCL-2 Family Reunion","volume":"37","author":"Chipuk","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: Opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","first-page":"55","article-title":"Growth-inhibitory effects of curcumin on ovary cancer cells and its mechanisms","volume":"24","author":"Zheng","year":"2004","journal-title":"J. Huazhong Univ. Sci. Technol.-Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, M.J., Park, K.S., Kim, K.T., and Gil, E.Y. (2020). The inhibitory effect of curcumin via fascin suppression through JAK\/STAT3 pathway on metastasis and recurrence of ovary cancer cells. BMC Women\u2019s Health, 20.","DOI":"10.1186\/s12905-020-01122-2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9692656","DOI":"10.1155\/2024\/9692656","article-title":"Anticancer and Antioxidant Properties of Vernonia amygdalina Delile and Citrus aurantifolia (Christm.) Swingle Juice Extracts: An In Vitro Study","volume":"2024","author":"Dotse","year":"2024","journal-title":"BioMed Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141556","DOI":"10.1095\/biolreprod.116.141556","article-title":"Luteolin inhibits proliferation and induces apoptosis of human placental choriocarcinoma cells by blocking the PI3K\/AKT pathway and regulating sterol regulatory element binding protein activity","volume":"95","author":"Lim","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1042\/bj2860331","article-title":"Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation","volume":"286","author":"Cohen","year":"1992","journal-title":"Biochem. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:28:51Z","timestamp":1788928131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177887"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177887","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}