Open Access

Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells

  • Authors:
    • Sung‑Hyun Kim
    • Gang‑Sik Choo
    • Eun‑Seon Yoo
    • Joong‑Seok Woo
    • So‑Hee Han
    • Jae‑Han Lee
    • Ji‑Youn Jung
  • View Affiliations

  • Published online on: August 28, 2019     https://doi.org/10.3892/or.2019.7295
  • Pages: 1904-1914
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti‑inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration‑dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose‑dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin‑induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)‑JNK and p‑p38, and cleaved poly‑ADP ribose polymerase, and decreased the levels of Bcl‑2 and p‑ERK1/2 in a concentration‑dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor‑inhibitory effect. Immunohistochemical staining revealed elevated expression of p‑JNK and p‑p38 as well as reduced expression of p‑ERK1/2 associated with silymarin‑treatment. Silymarin was revealed to reduce tumor growth through inhibition of p‑ERK and activation of p‑p38 and p‑JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.
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November-2019
Volume 42 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim SH, Choo GS, Yoo ES, Woo JS, Han SH, Lee JH and Jung JY: Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncol Rep 42: 1904-1914, 2019
APA
Kim, S., Choo, G., Yoo, E., Woo, J., Han, S., Lee, J., & Jung, J. (2019). Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncology Reports, 42, 1904-1914. https://doi.org/10.3892/or.2019.7295
MLA
Kim, S., Choo, G., Yoo, E., Woo, J., Han, S., Lee, J., Jung, J."Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells". Oncology Reports 42.5 (2019): 1904-1914.
Chicago
Kim, S., Choo, G., Yoo, E., Woo, J., Han, S., Lee, J., Jung, J."Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells". Oncology Reports 42, no. 5 (2019): 1904-1914. https://doi.org/10.3892/or.2019.7295