Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells

Chen, Huei-Mei; Wu, Yang-Chang; Chia, Yi-Chen; Chang, Fang-Rong; Hsu, Hseng-Kuang; Hsieh, Ya-Ching; Chen, Chih-Chen; Yuan, Shyng-Shiou

doi:10.1016/j.canlet.2009.05.040

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Volume 286, Issue 2 , Pages 161-171, 28 December 2009

Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells

Huei-Mei Chen
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
- Department of Medical Research, E-DA Hospital, Kaohsiung 824, Taiwan, ROC
Yang-Chang Wu
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
Yi-Chen Chia
- Department of Food Science and Technology, Tajen University, Pingtung 907, Taiwan, ROC
Fang-Rong Chang
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
Hseng-Kuang Hsu
- Department of Physiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
Ya-Ching Hsieh
- Department of Medical Research, E-DA Hospital, Kaohsiung 824, Taiwan, ROC
Chih-Chen Chen
- Department of Obstetrics and Gynecology, E-DA Hospital, Kaohsiung 824, Taiwan, ROC
- Corresponding authors. Address: Department of Medical Research and Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, 1, E-DA Road, Jiau-Shu Tsuen, Yan-Chau Shiang, Kaohsiung County, Taiwan 824, ROC. Tel.: +886 7 6151100x5901; fax: +886 7 6155352 (S.-S. Yuan).
Shyng-Shiou Yuan
- Department of Medical Research, E-DA Hospital, Kaohsiung 824, Taiwan, ROC
- Department of Obstetrics and Gynecology, E-DA Hospital, Kaohsiung 824, Taiwan, ROC
- Department of Biological Science and Technology, I-Shou University, Kaohsiung 824, Taiwan, ROC
- Corresponding authors. Address: Department of Medical Research and Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, 1, E-DA Road, Jiau-Shu Tsuen, Yan-Chau Shiang, Kaohsiung County, Taiwan 824, ROC. Tel.: +886 7 6151100x5901; fax: +886 7 6155352 (S.-S. Yuan).

Received 10 January 2009; received in revised form 6 May 2009; accepted 25 May 2009. published online 09 July 2009.

Abstract

Prostate cancer, the most frequently diagnosed malignancy in elderly males of the United States, has become a major health issue in Asia. Previous studies have demonstrated that leaf extracts of Toona sinensis Roem. contain cytotoxic activity on several cancer cells including prostate cancer cells. In this study, gallic acid is identified as the major anti-cancer compound in T. sinensis leaf extracts. It is cytotoxic to DU145 prostate cancer cells, through generation of reactive oxygen species (ROS) and mitochondria-mediated apoptosis, which were reversed by antioxidants catalase and N-acetylcysteine. Furthermore, gallic acid is shown to block the growth of DU145 cells at G2/M phases by activating Chk1 and Chk2 and inhibiting Cdc25C and Cdc2 activities. In addition, gallic acid has a synergistic effect with doxorubicin in suppressing the growth of DU145 cells. Taken together, our results suggest that gallic acid has the potential to be developed into an anti-prostate cancer drug and is worthy of further studies.

Keywords: Prostate cancer, Toona sinensis, Gallic acid, Cytotoxicity, G2/M phase