SM22α inhibits cell proliferation and protects against anticancer drugs and γ-radiation in HepG2 cells: Involvement of metallothioneins

Kim, Tae Rim; Moon, Ji Hye; Lee, Hee Min; Cho, Eun Wie; Paik, Sang Gi; Kim, In Gyu

doi:10.1016/j.febslet.2009.09.040

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Volume 583, Issue 20 , Pages 3356-3362, 20 October 2009

SM22α inhibits cell proliferation and protects against anticancer drugs and γ-radiation in HepG2 cells: Involvement of metallothioneins

Edited by Angel Nebrada

Tae Rim Kim
- Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejeon 305-600, Republic of Korea
- Department of Biology, School of Biosciences and Biotechnology, and the Institute of Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea
Ji Hye Moon
- Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejeon 305-600, Republic of Korea
Hee Min Lee
- Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejeon 305-600, Republic of Korea
Eun Wie Cho
- Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusong, Daejeon 305-333, Republic of Korea
Sang Gi Paik
- Department of Biology, School of Biosciences and Biotechnology, and the Institute of Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea
In Gyu Kim
- Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejeon 305-600, Republic of Korea
- Corresponding author. Fax: +82 42 861 9560.

Received 26 August 2009; received in revised form 21 September 2009; accepted 23 September 2009. published online 30 September 2009.

Abstract

Smooth muscle protein 22-alpha (SM22α) has been postulated to affect the structure and function of the actin filament. In this study, we report on the significant induction of SM22α by cytotoxic agents in HepG2 cells. SM22α-overexpression inhibited the activation of IGF-1Rβ/Akt and Erk, consequently suppressing cell proliferation. On the other hand, SM22α-overexpressing cells became resistant to apoptotic cell death caused by cytotoxic agents, in which metallothionein (MT) isoforms, especially MT1G, were significantly induced. MT1G-overexpression also conferred cellular resistance, and SM22α regulated the expression of MT1G at a transcriptional level. This study provides the first demonstration of SM22α-induced blockage of cell proliferation and cellular resistance to overcome the detrimental effects of damaging agents.

Keywords: SM22α, Luteolin, Cytotoxic drug, IGF-1Rβ/Akt, Metallothionein