alexa Down-Regulation of MutS Homolog 2 (MSH2) Expression by Curcumin Enhances Cytotoxicity Induced by Gemcitabine in Human Lung Adenocarcinoma Cells | OMICS International| Abstract
ISSN: 2161-1165

Epidemiology: Open Access
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  • Research Article   
  • Epidemiology (Sunnyvale) 2017, Vol 7(6): 332
  • DOI: 10.4172/2161-1165.1000332

Down-Regulation of MutS Homolog 2 (MSH2) Expression by Curcumin Enhances Cytotoxicity Induced by Gemcitabine in Human Lung Adenocarcinoma Cells

Jen-Chung Ko1, Yi-Shuan Peng2#, Chia-Hung Wu2#, Jyh-Cheng Chen3, Hao-Yu Zheng2, Yuan-Cheng Lin2, Peng-Fang Ma2, Wen-Ching Chen2 and Yun-Wei Lin2*
1Department of Internal Medicine, National Taiwan University Hospital, , Hsin-Chu Branch, Taiwan
2Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
3Department of Food Science, National Chiayi University, Chiayi, Taiwan
#Contributed equally to this work
*Corresponding Author : Yun-Wei Lin, Department of Biochemical Science and Technology, National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan, Tel: 886-5-271-7770, Email: [email protected]

Received Date: Nov 17, 2017 / Accepted Date: Dec 01, 2017 / Published Date: Dec 11, 2017

Abstract

Gemcitabine (2′,2′-difluorodeoxycytidine) is a difluorinated analog of deoxycytidine. It is used clinically to treat patients with non-small-cell lung cancer (NSCLC). Curcumin is a yellow pigment derived from the rhizome of Curcuma longa, and has been proven to have antioxidant and antitumor properties. Human MutS homolog 2 (MSH2) is a key DNA mismatch repair protein that plays an important role in maintaining genomic stability. Depletion of MSH2 from cells can reverse resistance to certain DNA-damaging agents. In this study, exposure of human lung adenocarcinoma A549 and H1975 cells to gemcitabine increased protein phosphorylation of MKK3/6 and p38 MAPK in a time- and dose-dependent manner; this was accompanied by increased expression of MSH2 mRNA and protein. Gemcitabine-induced cytotoxicity was significantly enhanced by MSH2 siRNA transfection or inactivation of p38 MAPK by SB202190 or p38 MAPK siRNA transfection. However, overexpression of MSH2 cDNA reduced gemcitabine-induced cytotoxicity. Furthermore, curcumin enhanced gemcitabine-induced cytotoxicity via inactivation of MKK3/6-p38 MAPK and downregulation of MSH2. Enforced expression of constitutively active MKK6 rescued cell viability and restored MSH2 protein levels that were suppressed by curcumin and gemcitabine. Suppression of MSH2 expression and a combination with curcumin may be considered as potential therapeutic modalities for gemcitabine-resistant NSCLC cells.

Keywords: Gemcitabine; Curcumin; MSH2; p38 MAPK; Non-small cell lung cancer

Citation: Ko JC, Peng YS, Wu CH, Chen JC, Zheng HY, et al. (2017) Down-Regulation of MutS Homolog 2 (MSH2) Expression by Curcumin Enhances Cytotoxicity Induced by Gemcitabine in Human Lung Adenocarcinoma Cells. Epidemiol 7:332. Doi: 10.4172/2161-1165.1000332

Copyright: © 2017 Jen-Chung Ko, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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