(-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer
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Qingyuan Yang1, Jianchun Wu2, Yingbin Luo2, Nan Huang1, Ni Zhen1, Yun Zhou1, Fenyong Sun1, Zhi Li3, Qiuhui Pan4,*, Yan Li2,*
1Department of Clinical Laboratory Medicine, Tenth People’s Hospital of Tongji University, Shanghai, 200072, China
2Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
3Department of Clinical Laboratory Medicine, Yangpu Hospital of Tongji University, Shanghai, 200090, China
4Central Laboratory, Tenth People’s Hospital of Tongji University, Shanghai, 200072, China
*The first two authors equally contributed to this work
Yan Li, email: [email protected]
Qiuhui Pan, email: [email protected]
Keywords: (-)-Guaiol, RAD51, autophagy, chemosensitivity, DSBs
Received: April 26, 2016 Accepted: August 11, 2016 Published: August 23, 2016
(-)-Guaiol, generally known as an antibacterial compound, has been found in many medicinal plants. Its roles in tumor suppression are still under investigation. In the study, we mainly focused on exploring its applications in dealing with non-small cell lung cancer (NSCLC) and the underlying mechanisms. Here, we show that (-)-Guaiol significantly inhibits cell growth of NSCLC cells both in vitro and in vivo. Further high throughput analysis reveals that RAD51, a pivotal factor in homologous recombination repair, is a potential target for it. The following mechanism studies show that (-)-Guaiol is involved in cell autophagy to regulate the expression of RAD51, leading to double-strand breaks triggered cell apoptosis. Moreover, targeting RAD51, which is highly overexpressed in the lung adenocarcinoma tissues, can significantly increase the chemosensitivity of NSCLC cells to (-)-Guaiol both in vitro and in vivo. All in all, our studies provide an attractive insight in applying (-)-Guaiol into NSCLC treatments and further suggest that knockdown of oncogenic RAD51 will greatly enhance the chemosensitivity of patients with NSCLC.
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