Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8(8):14268.

Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells

Ming-Ju Hsieh _, Chiao-Wen Lin, Hui-Ling Chiou, Shun-Fa Yang and Mu-Kuan Chen

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Oncotarget. 2015; 6:30831-30849. https://doi.org/10.18632/oncotarget.5036

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Abstract

Ming-Ju Hsieh1,2,3, Chiao-Wen Lin4,5, Hui-Ling Chiou6,7, Shun-Fa Yang3,8, Mu-Kuan Chen9

1Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan

2School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan

3Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

4Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan

5Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

6School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan

7Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

8Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

9Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan

Correspondence to:

Mu-Kuan Chen, e-mail: 53780@cch.org.tw

Shun-Fa Yang, e-mail: ysf@csmu.edu.tw

Keywords: dehydroandrographolide, autophagy, p53, MAPK, oral cancer

Received: March 31, 2015     Accepted: August 24, 2015     Published: September 03, 2015

ABSTRACT

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.


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