{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T13:41:41Z","timestamp":1788010901103,"version":"build-2784847793"},"reference-count":60,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation Research South Africa","award":["117898"],"award-info":[{"award-number":["117898"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Breast and colon cancers are leading causes of death worldwide. There is a need for improved treatment strategies. South African medicinal plants, including Clerodendrum glabrum (C. glabrum) and Combretum nelsonii (C. nelsonii), are known for their cytotoxic properties. This study aimed to isolate and characterize terpenoids and stilbenes from the roots of C. glabrum and C. nelsonii and evaluate their anticancer potential against colorectal adenocarcinoma (Caco-2) and hormone receptor-positive breast cancer (MCF-7) cell lines. Spectroscopic techniques including nuclear magnetic resonance spectroscopy (NMR) were used to characterize the isolated compounds. Repeated column chromatography of C. glabrum extract led to the isolation of ferruginol (1), royleanone (2), and \u03b2-amyrin palmitate (3). C. nelsonii extract afforded combretastatin A-1 (4), a mixture of combretastatin A-1-2\u2032-O-\u03b2-D-glucopyranoside (5a) and combretastatin B-1-2\u2032-O-\u03b2-D-glucopyranoside (5b). Compounds 1, 2, 4, 5a, and 5b were isolated for the first time from the plant species. C. glabrum extract showed good anticancer properties with LC50 of 1.30 \u00d7 103 \u00b5g\/mL (CaCo-2) and 2790 \u00b5g\/mL (MCF-7). Compound (1) exhibited high toxicity against the Caco-2 at LC50 of 24.3 \u00b5g\/mL and moderate activity against MCF-7 at 48.4 \u00b5g\/mL. Compound (4) and the mixture (5a and 5b) showed moderate activity against the MCF-7 at LC50 72.0 and 44.1 \u00b5g\/mL, respectively. These findings highlight C. glabrum and C. nelsonii as promising sources of anticancer lead compounds.<\/jats:p>","DOI":"10.3390\/plants14182832","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:51:46Z","timestamp":1757577106000},"page":"2832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytotoxic Activity of Chemical Constituents of Clerodendrum glabrum and Combretum nelsonii Root Extracts Against Selected Cancer Cell Lines"],"prefix":"10.3390","volume":"14","author":[{"given":"Kopelo V.","family":"Mabunda","sequence":"first","affiliation":[{"name":"Department of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-128X","authenticated-orcid":false,"given":"Douglas","family":"Kemboi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"},{"name":"School of Science and Technology, University of Kabianga, P.O. Box 2030, Kericho 20200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8144-1331","authenticated-orcid":false,"given":"Ibukun M.","family":"Famuyide","sequence":"additional","affiliation":[{"name":"Phytomedicine Programme, Department of Paraclinical Sciences, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-0613","authenticated-orcid":false,"given":"Lyndy J.","family":"McGaw","sequence":"additional","affiliation":[{"name":"Phytomedicine Programme, Department of Paraclinical Sciences, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ntebogeng S.","family":"Mokgalaka-Fleischmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuyelwa Jacqueline","family":"Tembu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","unstructured":"(2023, August 18). World Health Organization (WHO), Available online: https:\/\/www.statssa.gov.za\/publications\/03-08-00\/03-08-002023.pdf."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4314\/ahs.v21i1.8","article-title":"Clustering time trends of breast cancer incidence in Africa: A 27-year longitudinal study in 53 countries","volume":"21","author":"Saberian","year":"2021","journal-title":"Afr. Health Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e055735","DOI":"10.1136\/bmjopen-2021-055735","article-title":"Triple-negative breast cancer prevalence in Africa: A systematic review and meta-analysis","volume":"12","author":"Hercules","year":"2022","journal-title":"BMJ Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cassiem, W., and De Kock, M. (2019). The anti-proliferative effect of apricot and peach kernel extracts on human colon cancer cells in vitro. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2437-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118","DOI":"10.7196\/SAMJ.2018.v108i2.12338","article-title":"Colorectal cancer in South Africa: An assessment of disease presentation, treatment pathways and 5-year survival","volume":"108","author":"Brand","year":"2018","journal-title":"S. Afr. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12967-024-06033-6","article-title":"mRNA vaccines in the context of cancer treatment: From concept to application","volume":"23","author":"Fu","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cancergen.2024.06.002","article-title":"Cancer treatments: Past, present, and future","volume":"287","author":"Sonkin","year":"2024","journal-title":"Cancer Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41392-024-01856-7","article-title":"Exploring treatment options in cancer: Tumor treatment strategies","volume":"9","author":"Liu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1245\/s10434-019-08042-y","article-title":"Utilization of adjuvant radiotherapy for resected colon cancer and its effect on outcome","volume":"27","author":"Wegner","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"131120","DOI":"10.1016\/j.cej.2021.131120","article-title":"Homotypic biomimetic coating synergizes chemo-photothermal combination therapy to treat breast cancer overcoming drug resistance","volume":"428","author":"Guo","year":"2022","journal-title":"J. Chem. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153402","DOI":"10.1016\/j.phymed.2020.153402","article-title":"Protection against chemotherapy and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals","volume":"80","author":"Liu","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stoicescu, E.A., Burcea, M., Iancu, R.C., Zivari, M., Popa Cherecheanu, A., Bujor, I.A., Rastoaca, C., and Iancu, G. (2021). Docetaxel for breast cancer treatment side effects on ocular surface, a systematic review. Processes, 9.","DOI":"10.3390\/pr9071086"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jep.2016.04.005","article-title":"Cytotoxicity of South-African medicinal plants towards sensitive and multidrug-resistant cancer cells","volume":"186","author":"Saeed","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","first-page":"101","article-title":"A taxonomic revision of the Genus Clerodendrum L. (Verbenaceae) in Australia","volume":"11","author":"Munir","year":"1989","journal-title":"J. Adelaide Bot. Gard."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/tax.591013","article-title":"Further disintegration and redefinition of Clerodendrum (Lamiaceae): Implications for the understanding of the evolution of an intriguing breeding strategy","volume":"59","author":"Yuan","year":"2010","journal-title":"Taxon"},{"key":"ref_20","unstructured":"(2023, August 18). Clerodendron glabrum | PlantZAfrica. Available online: http:\/\/pza.sanbi.org\/clerodendron-glabrum."},{"key":"ref_21","unstructured":"Watt, J.M., and Breyer-Brandwijk, M.G. (1962). The Medicinal and Poisonous Plants of Southern and Eastern Africa, E. & S. Livingstone Ltd."},{"key":"ref_22","unstructured":"Quattrocchi, U. (2012). CRC World Dictionary of Medicinal and Poisonous Plants II C-D, CRC Press. [1st ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jadeja, R., Thounaojam, M., Ramachandran, A.V., and Devkar, R. (2009). Phytochemical Constituents and Free Radical Scavenging Activity of Clerodendron glandulosum.Coleb Methanolic Extract. J. Complement. Integr. Med., 6.","DOI":"10.2202\/1553-3840.1226"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1002\/hlca.201200552","article-title":"Clerodendrumic Acid, a new triterpenoid from Clerodendrum glabrum (Verbenaceae), and antimicrobial activities of fractions and constituents","volume":"96","author":"Masevhe","year":"2013","journal-title":"Helv. Chim. Acta"},{"key":"ref_25","first-page":"2051","article-title":"Phytochemical, and biological studies of Clerodendrum glabrum leaves","volume":"28","author":"Fouad","year":"2013","journal-title":"Int. J. Pharmacog. Phytochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.sajb.2020.07.009","article-title":"Cytotoxicity of triterpenoids from Clerodendrum glabrum against triple negative breast cancer cells in vitro","volume":"133","author":"Teclegeorgish","year":"2020","journal-title":"S. Afr. J. Bot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1021\/acs.jnatprod.3c00743","article-title":"Isolation and in vitro and in vivo activity of secondary metabolites from Clerodendrum polycephalum baker against plasmodium malaria parasites","volume":"86","author":"Tamuli","year":"2023","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105338","DOI":"10.1016\/j.arabjc.2023.105338","article-title":"Cyclohexylethanoid derivative and rearranged abietane diterpenoids with anti-inflammatory activities from Clerodendrum bungei and C. inerme","volume":"17","author":"Wu","year":"2024","journal-title":"Arab. J. Chem."},{"key":"ref_29","first-page":"1","article-title":"Phytochemical screening and antimicrobial activity of Clerodendrum viscosum leaf extracts","volume":"8","author":"Penu","year":"2022","journal-title":"Jagannath Univ. J. Life Earth Sci."},{"key":"ref_30","first-page":"100121","article-title":"Phytochemical compositions, antioxidant, anticholinesterase, and antibacterial properties of Clerodendrum thomsoniae Balf. f. leaves: In vitro and in silico analyses","volume":"5","author":"Bhattacharyya","year":"2024","journal-title":"Nat. Prod. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hossain, M.M., Roy, N., and Islam, F. (2025). Exploring the phytochemical composition, antioxidant properties, and anticancer mechanism of Clerodendrum viscosum vent. A comprehensive review. Curr. Tradit. Med., 1\u201316.","DOI":"10.2174\/0122150838357493250122122451"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2307\/2399158","article-title":"The order myrtales: Circumscription, variation, and relationships","volume":"71","author":"Dahlgren","year":"1984","journal-title":"Ann. Mo. Bot. Gard."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0378-8741(00)00405-0","article-title":"An investigation on the biological activity of Combretum species","volume":"75","author":"McGaw","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","first-page":"3416","article-title":"Combretum quadrangulare (Combretaceae): Phytochemical constituents and biological activity","volume":"4","author":"Roy","year":"2014","journal-title":"Indo Am. J. Pharm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sil\u00e9n, H., Salih, E.Y., Mgbeahuruike, E.E., and Fyhrqvist, P. (2023). Ethnopharmacology, antimicrobial potency, and phytochemistry of African Combretum and Pteleopsis species (Combretaceae): A review. Antibiotics, 12.","DOI":"10.3390\/antibiotics12020264"},{"key":"ref_36","unstructured":"Stace, C.A. (2007). The families and genera of vascular plants. Flowering Plants Eudicots, Springer. [1st ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.sajb.2006.09.010","article-title":"The antifungal activity of twenty-four southern african Combretum species (Combretaceae)","volume":"73","author":"Masoko","year":"2007","journal-title":"S. Afr. J. Bot."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1080\/14786410802267494","article-title":"Biological activity of two related triterpenes isolated from Combretum nelsonii (Combretaceae) leaves","volume":"22","author":"Masoko","year":"2008","journal-title":"Nat. Prod. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18063\/cp.v1i4.255","article-title":"Exploring the anticancer and anti-inflammatory activities of ferruginol in MCF-7 breast cancer cells","volume":"1","author":"Rengarajan","year":"2020","journal-title":"Cancer Plus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.joim.2017.12.004","article-title":"Cytotoxic activity of the chemical constituents of Clerodendrum indicum and Clerodendrum villosum roots","volume":"16","author":"Somwong","year":"2018","journal-title":"J. Integr. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1055\/s-2008-1074532","article-title":"New gastroprotective ferruginol derivatives with selective cytotoxicity against gastric cancer cells","volume":"74","author":"Espinoza","year":"2008","journal-title":"Planta Med."},{"key":"ref_42","first-page":"853","article-title":"Antimicrobial and antiparasitic abietane diterpenoids from the roots of Clerodendrum eriophyllum","volume":"5","author":"Machumi","year":"2010","journal-title":"Nat. Prod. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1177\/1534735414555806","article-title":"Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis","volume":"14","author":"Ho","year":"2015","journal-title":"Integr. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1076\/phbi.37.2.148.6082","article-title":"Cytotoxic activity of diterpenoids isolated from Salvia hypargeia","volume":"37","author":"Ulubelen","year":"2008","journal-title":"Pharmaceut. Biol."},{"key":"ref_45","first-page":"1055","article-title":"Royleanone diterpenoid exhibits potent anticancer effects in lncap human prostate carcinoma cells by inducing mitochondrial mediated apoptosis, cell cycle arrest, suppression of cell migration and down regulation of mTOR\/PI3K\/AKT signaling pathway","volume":"23","author":"Wu","year":"2018","journal-title":"J. BUON"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1211\/jpp.61.12.0015","article-title":"Gastroprotective effect and cytotoxicity of abietane diterpenes from the chilean lamiaceae Sphacele chamaedryoides (Balbis) Briq","volume":"61","author":"Areche","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4103\/pm.pm_265_20","article-title":"Anticancer activity of abietane diterpenoids from Salvia libanoticum grown in Lebanon","volume":"17","author":"Hijazi","year":"2021","journal-title":"Pharmacogn. Mag."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1046\/j.1365-2613.2002.00211.x","article-title":"The biology of the Combretastatins as tumour vascular targeting agents","volume":"83","author":"Tozer","year":"2002","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1021\/jm000045a","article-title":"Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor hydroxyphenstatin and its sodium diphosphate prodrug","volume":"43","author":"Pettit","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_50","unstructured":"Akim, A. (2004). Biological Activities of Oryzanol, Stigmasterol and Microminutinin on Human Breast Cancer Cell-Line, MCF-7. [Ph.D. Thesis, University Putra Malaysia]."},{"key":"ref_51","first-page":"52","article-title":"Phytosterols from the stem bark of Combretum fragrans F. Hoffm","volume":"11","author":"Maima","year":"2008","journal-title":"East Cent. Afr. J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117021","DOI":"10.1016\/j.ejmech.2024.117021","article-title":"A novel life for antitumor combretastatins: Recent developments of hybrids, prodrugs, combination therapies, and antibody-drug conjugates","volume":"281","author":"Fantacuzzi","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.vph.2016.05.006","article-title":"Vascular disrupting activity of combretastatin analogues","volume":"83","author":"Salvador","year":"2016","journal-title":"Vasc. Pharmacol."},{"key":"ref_54","unstructured":"Patel, S., and Singh, A. (2018). Sterols and phytosterols in cancer prevention and therapy: Perspective. J. Food Biochem., 42."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yang, Y., He, P.Y., Zhang, Y., and Li, N. (2021). Natural products targeting the mitochondria in cancers. Molecules, 26.","DOI":"10.3390\/molecules26010092"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.biochi.2008.01.011","article-title":"Ferruginol suppresses survival signalling pathways in androgen-independent human prostate cancer cells","volume":"90","author":"Zambuzzi","year":"2008","journal-title":"Biochimie"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8094","DOI":"10.1021\/acsomega.9b00512","article-title":"Cytotoxic activity of royleanone diterpenes from Plectranthus madagascariensis Benth","volume":"4","author":"Matias","year":"2019","journal-title":"ACS Omega"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Karatoprak, G.\u015e., K\u00fcpeli Akkol, E., Gen\u00e7, Y., Bardakc\u0131, H., Y\u00fccel, \u00c7., and Sobarzo-S\u00e1nchez, E. (2020). Combretastatins: An overview of structure, probable mechanisms of action and potential applications. Molecules, 25.","DOI":"10.3390\/molecules25112560"},{"key":"ref_60","unstructured":"Li, Y., Wang, R., and Xie, H. (2021). Stigmasterol sensitizes hepatocellular carcinoma cells to sorafenib by inducing ROS-mediated apoptosis and autophagy. Biomed. Pharmacother., 135."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/18\/2832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:43:34Z","timestamp":1760035414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/18\/2832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":60,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["plants14182832"],"URL":"https:\/\/doi.org\/10.3390\/plants14182832","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]}}}