Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells

G. Ramakrishnan, L. Lo Muzio, C. M. Elinos-Báez, S. Jagan, T. A. Augustine, S. Kamaraj, P. Anandakumar, T. Devaki

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Objectives: The aim of this study was to investigate mechanisms involved in the growth inhibitory effect of silymarin, in humanhepatocellular carcinoma. Materials and Methods: The human hepatocellular carcinoma cell line HepG2 was utilized and the MTT assay was performed to study the antiproliferative effect of silymarin. Dual staining was undertaken for ethidium bromide/acridine orange, propidium iodide staining and DNA fragmentation studies were executed to confirm the presence of apoptosis. Cell-cycle analysis was revealed by flow cytometry and mitochondrial transmembrane potential was measured by uptake of the mitochondrial-specific lipophilic cationic dye rhodamine 123. Western blotting analysis for cytochrome c, p53, Bax, Bcl-2, APAF-1, caspase-3, survivin, β-catenin, cyclin D1, c-Myc and PCNA was carried out. Results: Silymarin inhibited population growth of the hepatocellular carcinoma cells in a dose-dependent manner, and the percentage of apoptotic cells was increased after treatment with 50 and 75 g/ml silymarin for 24 h. Silymarin treatment increased the proportion of cells with reduced DNA content (sub-G 0/G1 or A0 peak), indicative of apoptosis with loss of cells in the G1 phase. Silymarin also decreased mitochondrial transmembrane potential of the cells, thereby increasing levels of cytosolic cytochrome c while up-regulating expression of pro-apoptotic proteins (such as p53, Bax, APAF-1 and caspase-3) with concomitant decrease in anti-apoptotic proteins (Bcl-2 and survivin) and proliferation-associated proteins (β-catenin, cyclin D1, c-Myc and PCNA). Conclusions: Our results demonstrate that silymarin treatment inhibited proliferation and induced apoptosis in the human hepatocellular carcinoma cell line HepG2.

Original languageEnglish (US)
Pages (from-to)229-240
Number of pages12
JournalCell Proliferation
Volume42
Issue number2
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Cell Biology

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    Ramakrishnan, G., Lo Muzio, L., Elinos-Báez, C. M., Jagan, S., Augustine, T. A., Kamaraj, S., Anandakumar, P., & Devaki, T. (2009). Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells. Cell Proliferation, 42(2), 229-240. https://doi.org/10.1111/j.1365-2184.2008.00581.x