title: Trigonella foenum (Fenugreek) Induced Apoptosis in Hepatocellular Carcinoma Cell Line, HepG2, Mediated by Upregulation of p53 and Proliferating Cell Nuclear Antigen.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and most current therapies are of limited efficacy. Trigonella foenum (Fenugreek) is a traditional herbal plant with antitumor activity, although the mechanisms of its activity remain unclear. Herein, a crude methanol extract was prepared from Fenugreek seeds (FCE) and its anticancer mechanism was evaluated, using HepG2 cell line. Growth-inhibitory effect and apoptosis induction of HepG2 cells were evidenced by MTT assay, cell morphology alteration, apoptosis enzyme-linked immunosorbent assay, flow cytometric analysis, caspase-3 activity, and expression of p53, proapoptotic protein, Bax, and proliferating cell nuclear antigen (PCNA) after (100 ∼ 500 μg/mL) FCE treatment for 48 h. Furthermore, FCE was analyzed by Chromatography-Mass Spectrometry (GC/MS). Our results revealed that FCE treatment for 48 h showed a cytotoxic effect and apoptosis induction in a dose-dependent manner that was mediated by upregulation of p53, Bax, PCNA, and caspase-3 activation in HepG2 cells. GC-MS analysis of FCE showed the presence of fourteen bioactive compounds such as Terpenoids and Flavonoids, including two main constituents with anticancer activity, Squalene and Naringenin (27.71% and 24.05%), respectively. Our data introduced FCE as a promising nontoxic herbal with therapeutic potential to induce apoptosis in HepG2 cells through p53, Bax, and PCNA upregulation in caspase-3 dependent manner.
authors.affiliation: Zoology Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
authors.forename: Mahmoud I M
authors.initials: MI
authors.lastname: Khalil
authors.affiliation: Botany and Microbiology Department, Science College, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia ; Botany and Microbiology Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Ibrahim
authors.affiliation: Botany and Microbiology Department, Science College, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Gehan A
authors.initials: GA
authors.lastname: El-Gaaly
authors.affiliation: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Sultan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D029910:Trigonella / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53