{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:26:04Z","timestamp":1791296764758,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2011,4,6]],"date-time":"2011-04-06T00:00:00Z","timestamp":1302048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Liver cancer has become one of the major types of cancer with high mortality and liver cancer is not responsive to the current cytotoxic agents used in chemotherapy. The purpose of this study was to examine the in vitro cytotoxicity of goniothalamin on human hepatoblastoma HepG2 cells and normal liver Chang cells. The cytotoxicity of goniothalamin against HepG2 and liver Chang cell was tested using MTT cell viability assay, LDH leakage assay, cell cycle flow cytometry PI analysis, BrdU proliferation ELISA assay and trypan blue dye exclusion assay. Goniothalamin selectively inhibited HepG2 cells [IC50 = 4.6 (\u00b10.23) \u00b5M in the MTT assay; IC50 = 5.20 (\u00b10.01) \u00b5M for LDH assay at 72 hours], with less sensitivity in Chang cells [IC50 = 35.0 (\u00b10.09) \u00b5M for MTT assay; IC50 = 32.5 (\u00b10.04) \u00b5M for LDH assay at 72 hours]. In the trypan blue dye exclusion assay, the Viability Indexes were 52 \u00b1 1.73% for HepG2 cells and 62 \u00b1 4.36% for Chang cells at IC50 after 72 hours. Cytotoxicity of goniothalamin was related to inhibition of DNA synthesis, as revealed by the reduction of BrdU incorporation. At 72 hours, the lowest concentration of goniothalamin (2.3 \u00b5L) retained 97.6% of normal liver Chang cells proliferation while it reduced HepG2 cell proliferation to 19.8% as compared to control. Besides, goniothalamin caused accumulation of hypodiploid apoptosis and different degree of G2\/M arrested as shown in cell cycle analysis by flow cytometry. Goniothalamin selectively killed liver cancer cell through suppression of proliferation and induction of apoptosis. These results suggest that goniothalamin shows potential cytotoxicity against hepatoblastoma HepG2 cells.<\/jats:p>","DOI":"10.3390\/molecules16042944","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T20:09:10Z","timestamp":1317154150000},"page":"2944-2959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Selective Cytotoxicity of Goniothalamin against Hepatoblastoma HepG2 Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Mothanna","family":"Al-Qubaisi","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosli","family":"Rozita","sequence":"additional","affiliation":[{"name":"Department of Obstetric and Gynaecology, Faculty of Medicine and Health Sciences, University Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swee-Keong","family":"Yeap","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul-Rahman","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul-Manaf","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Biotechnology, University Sultan Zainal Abidin (UniSZA), Kampus Kota, Jalan Sultan Mahmud, 20400 Kuala Terengganu, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noorjahan B.","family":"Alitheen","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1056\/NEJM199903113401001","article-title":"Rising incidence of hepatocellular carcinoma in the United States","volume":"340","author":"Mason","year":"1999","journal-title":"New. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1034\/j.1600-0676.2000.020004312.x","article-title":"Hepatocellular carcinoma in Germany: A retrospective epidemiological study from a low-endemic area","volume":"20","author":"Kubicka","year":"2000","journal-title":"Liver"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1093\/jnci\/84.4.262","article-title":"Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular carcinoma","volume":"84","author":"Huang","year":"1992","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/bjc.1998.126","article-title":"p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation","volume":"77","author":"Honda","year":"1998","journal-title":"Br. J. Cancer"},{"key":"ref_5","first-page":"2501","article-title":"Determination of the oncogenes p53 and C-Erb B2 in the tumour cytosols of advanced hepatocellular carcinoma (HCC) and correlation to survival time","volume":"19","author":"Heinze","year":"1999","journal-title":"Anticancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/qjmed\/91.12.821","article-title":"Tumor ablation and hepatic decompensation rates in multi\u2013agent chemoembolization of hepatocellular carcinoma","volume":"91","author":"Shah","year":"1998","journal-title":"QJM"},{"key":"ref_7","unstructured":"Mehta, D.K. (2006). British National Formulary, Pharmaceutical Press. [52nd ed.]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1016\/S0040-4039(00)95462-5","article-title":"Goniothalamin oxide: An embryotoxic compound from Goniothalamus macrophyllus (Annonaceae)","volume":"28","author":"Sam","year":"1987","journal-title":"Tetrahedron Lett."},{"key":"ref_9","first-page":"479","article-title":"Goniothalamin, a cytotoxic compound, isolated from Goniothalamus macrophyllus (Blume) Hook. f. & Thomson var","volume":"27","author":"Chatchai","year":"2005","journal-title":"macrophyllus. Songklanakarin. J. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ejphar.2005.08.047","article-title":"Goniothalamin induces cell cycle-specific apoptosis by modulating the redox status in MDA-MB-231 cells","volume":"522","author":"Chen","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1016\/j.bmc.2005.02.007","article-title":"(R)- Goniothalamin: Total syntheses and cytotoxic activity against cancer cell lines","volume":"13","author":"Kohn","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"ref_12","unstructured":"Newall, C.A., Anderson, L.A., and Phillipson, J.D. (1996). Herbal Medicines. A Guide for Health-care Professionals, Pharmaceutical Press."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schulz, V., Rudolf, H., and Tyler, V.E. (1998). Rational Phytotherapy. A Physician\u2019s Guide to Herbal Medicine, Springer. [3rd ed.].","DOI":"10.1007\/978-3-642-97704-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0093-7754(01)90034-X","article-title":"Proteasome inhibition in cancer: Development of PS-341","volume":"28","author":"Adams","year":"2001","journal-title":"Sem. Oncol."},{"key":"ref_15","first-page":"1739","article-title":"Non-steroid receptor mediated antiproliferative activity of styrylpyrone derivative (SPD) in human breast cancer cell lines","volume":"18","author":"Pihie","year":"1998","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jhep.2004.07.015","article-title":"Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest in human hepatocellular carcinoma cells and enhance chemosensitivity to paclitaxel, docetaxel, doxorubicin and the Bcl-2 inhibitor HA14-1","volume":"41","author":"Andreas","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nm0196-72","article-title":"Loss of normal p53 function confers sensitization to Taxol by increasing G2\/M arrest and apoptosis","volume":"2","author":"Wahl","year":"1996","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s00280-001-0376-4","article-title":"Doxorubicin-induced apoptosis and chemosensitivity in hepatoma cell lines","volume":"49","author":"Lee","year":"2002","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1126\/science.7123245","article-title":"Monoclonal antibody to 5-bromo- and 5- Iododeoxyuridine: A new reagent for detection of DNA replication","volume":"218","author":"Gratzner","year":"1982","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cbi.2005.10.107","article-title":"Goniothalamin induces apoptosis in vascular smooth muscle cells","volume":"159","author":"Chan","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0887-2333(03)00051-1","article-title":"Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells","volume":"17","author":"Annuar","year":"2003","journal-title":"Toxicol. In Vitro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/jmv.1890300407","article-title":"Detection of integrated hepatitis B virus DNA in hepatocellular carcinoma cell lines by nonradioactive in situ hybridization","volume":"30","author":"Tay","year":"1990","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/sj.cdd.4400981","article-title":"Release of intact, monomeric cytochrome c from apoptotic and necrotic cells","volume":"9","author":"Jemmerson","year":"2002","journal-title":"Cell Death Differ."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/16\/4\/2944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:55:45Z","timestamp":1760219745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/16\/4\/2944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4,6]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2011,4]]}},"alternative-id":["molecules16042944"],"URL":"https:\/\/doi.org\/10.3390\/molecules16042944","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,6]]}}}