Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells

Sin,Seong; Kim,Sung  Young; Kim,Sung  Su

doi:10.3892/ijo.2012.1604

Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells

Authors:
- Seong Sin
- Sung Young Kim
- Sung Su Kim
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Affiliations: Department of Oriental Medicine, Kyung Hee University College of Oriental Medicine, Seoul 130‑701, Republic of Korea, Soram Cancer and Immunotherapy Research Center, Seoul 135-090, Republic of Korea
Published online on: August 23, 2012 https://doi.org/10.3892/ijo.2012.1604
Pages: 1669-1674

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Abstract

Therapy-induced senescence, an irreversible growth arrest, in cancer cells is regarded as a novel functional target that may improve cancer therapy. 20(S)-ginsenoside Rg3 [20(S)-Rg3], a chemical component extracted from Panax ginseng, has recently emerged as an effective anticancer medicine with evident antitumor effects and no observed toxic adverse reactions. We report here that chronic treatment with 20(S)-Rg3 in a sub-lethal concentration induced senescence-like growth arrest in human glioma cells. Glioma cells treated with 20(S)-Rg3 showed high expression of senescence-associated β-galactosidase, followed by upregulation of the CDK inhibitors p21 and p16. Moreover, reactive oxygen species (ROS) generation markedly increased in 20(S)-Rg3-treated cells compared with control cells. Consistently, co-incubation with the antioxidant N-acetyl cysteine interfered with 20(S)-Rg3-induced senescence in glioma cells. In addition, 20(S)-Rg3-induced-activation of Akt was associated with increased ROS levels, and depletion of Akt partially prevented 20(S)-Rg3-induced ROS generation and senescence induction in glioma cells. Furthermore, 20(S)-Rg3-induced senescence was partially rescued when the p53/p21 pathway was inactivated. Our data indicate that 20(S)-Rg3 induces senescence-like growth arrest in human glioma cancer through the Akt and p53/p21-dependent signaling pathways. This is the first report of a pro-senescent effect of 20(S)-Rg3 in cancer cells.

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