Trigonella Foenum (Fenugreek) Induced Apoptosis in Hepatocellular Carcinoma Cell Line, HepG2, Mediated by Upregulation of P53 and Proliferating Cell Nuclear Antigen

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Nov 12

PMID 26557712

Citations 18

Authors

Mahmoud I M Khalil

Mohamed M Ibrahim

Gehan A El-Gaaly

Ahmed S Sultan

Affiliations

Soon will be listed here.

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.

Citing Articles

Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines.

Khalifa A, Sheweita S, Namatalla A, Khalifa M, Nencioni A, Sultan A Cancers (Basel). 2025; 17(2).

PMID: 39857977 PMC: 11763687. DOI: 10.3390/cancers17020195.

Green-synthesized nanoparticles of the polyherbal extract attenuate the necrosis of pancreatic β-cell in a streptozotocin-induced diabetic model.

Hasan Chowdhury M, Al Araby S, Alelwani W, Kattan S, Mansouri O, Uddin Rahat M Heliyon. 2023; 9(5):e16137.

PMID: 37251822 PMC: 10208926. DOI: 10.1016/j.heliyon.2023.e16137.

Cell Growth Inhibition, DNA Fragmentation and Apoptosis-Inducing Properties of Household-Processed Leaves and Seeds of Fenugreek ( Linn.) against HepG2, HCT-116, and MCF-7 Cancerous Cell Lines.

Salam S, Rashed M, Ibrahim N, Rahim E, Alsufiani H, Mansouri R Curr Issues Mol Biol. 2023; 45(2):936-953.

PMID: 36826005 PMC: 9955320. DOI: 10.3390/cimb45020060.

Identification of hepatoprotective traditional Chinese medicines based on the structure-activity relationship, molecular network, and machine learning techniques.

He S, Yi Y, Hou D, Fu X, Zhang J, Ru X Front Pharmacol. 2022; 13:969979.

PMID: 36105213 PMC: 9465166. DOI: 10.3389/fphar.2022.969979.

Characterization of Possible α-Glucosidase Inhibitors from Extract Using LC-MS and In Silico Molecular Docking.

Elwekeel A, El Amir D, Mohamed E, Amin E, Hassan M, Zaki M Plants (Basel). 2022; 11(2).

PMID: 35050096 PMC: 8780848. DOI: 10.3390/plants11020208.

References

Khoja K, Shaf G, Hasan T, Syed N, Al-Khalifa A, Al-Assaf A . Fenugreek, a naturally occurring edible spice, kills MCF-7 human breast cancer cells via an apoptotic pathway. Asian Pac J Cancer Prev. 2012; 12(12):3299-304. View

Sultan A, Xie J, LeBaron M, Ealley E, Nevalainen M, Rui H . Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene. 2004; 24(5):746-60. DOI: 10.1038/sj.onc.1208203. View

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

McGlynn K, Tsao L, Hsing A, Devesa S, Fraumeni Jr J . International trends and patterns of primary liver cancer. Int J Cancer. 2001; 94(2):290-6. DOI: 10.1002/ijc.1456. View

Sun J, Liu R . Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer Lett. 2005; 241(1):124-34. DOI: 10.1016/j.canlet.2005.10.027. View

Maga G, Hubscher U . Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci. 2003; 116(Pt 15):3051-60. DOI: 10.1242/jcs.00653. View

Chang H, Lai Y, Cheng C, Ho J, Ding S, Liu Y . UV inducibility of rat proliferating cell nuclear antigen gene promoter. J Cell Biochem. 1999; 73(3):423-32. View

Kwon K, Barve A, Yu S, Huang M, Kong A . Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models. Acta Pharmacol Sin. 2007; 28(9):1409-21. DOI: 10.1111/j.1745-7254.2007.00694.x. View

Vijayan P, Vijayaraj P, Setty P, Hariharpura R, Godavarthi A, Badami S . The cytotoxic activity of the total alkaloids isolated from different parts of Solanum pseudocapsicum. Biol Pharm Bull. 2004; 27(4):528-30. DOI: 10.1248/bpb.27.528. View

10.

Guzman G, Alagiozian-Angelova V, Layden-Almer J, Layden T, Testa G, Benedetti E . p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients. Mod Pathol. 2005; 18(11):1498-503. DOI: 10.1038/modpathol.3800458. View

11.

Jacobson M, Weil M, Raff M . Programmed cell death in animal development. Cell. 1997; 88(3):347-54. DOI: 10.1016/s0092-8674(00)81873-5. View

12.

Kaviarasan S, Anuradha C . Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. Pharmazie. 2007; 62(4):299-304. View

13.

Bhatia K, Kaur M, Atif F, Ali M, Rehman H, Rahman S . Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food Chem Toxicol. 2006; 44(10):1744-50. DOI: 10.1016/j.fct.2006.05.013. View

14.

Boehme K, Dietz Y, Hewitt P, Mueller S . Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro. Toxicol Lett. 2010; 198(2):272-81. DOI: 10.1016/j.toxlet.2010.07.007. View

15.

Sultan A, Brim H, Sherif Z . Co-overexpression of Janus kinase 2 and signal transducer and activator of transcription 5a promotes differentiation of mammary cancer cells through reversal of epithelial-mesenchymal transition. Cancer Sci. 2008; 99(2):272-9. PMC: 11159878. DOI: 10.1111/j.1349-7006.2007.00685.x. View

16.

Maurya A, Vinayak M . Quercetin regresses Dalton's lymphoma growth via suppression of PI3K/AKT signaling leading to upregulation of p53 and decrease in energy metabolism. Nutr Cancer. 2015; 67(2):354-63. DOI: 10.1080/01635581.2015.990574. View

17.

Naryzhny S, Lee H . Observation of multiple isoforms and specific proteolysis patterns of proliferating cell nuclear antigen in the context of cell cycle compartments and sample preparations. Proteomics. 2003; 3(6):930-6. DOI: 10.1002/pmic.200300400. View

18.

Shishodia S, Aggarwal B . Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. Oncogene. 2005; 25(10):1463-73. DOI: 10.1038/sj.onc.1209194. View

19.

Peng S, Yang J, Xie P, Deng H, Li H, Feng D . [Expression of cyclins in hepatocellular carcinoma and its correlation to tumor cell apoptosis]. Ai Zheng. 2005; 24(6):695-8. View

20.

Yu Q . Restoring p53-mediated apoptosis in cancer cells: new opportunities for cancer therapy. Drug Resist Updat. 2006; 9(1-2):19-25. DOI: 10.1016/j.drup.2006.03.001. View