title: (-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer.
abstract: (-)-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.
authors: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Qingyuan
authors: Q
authors: Yang
authors: Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
authors: Jianchun
authors: J
authors: Wu
authors: Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
authors: Yingbin
authors: Y
authors: Luo
authors: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Nan
authors: N
authors: Huang
authors: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Ni
authors: N
authors: Zhen
authors: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Yun
authors: Y
authors: Zhou
authors: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Fenyong
authors: F
authors: Sun
authors: Department of Clinical Laboratory Medicine, Yangpu Hospital of Tongji University, Shanghai, 200090, China.
authors: Zhi
authors: Z
authors: Li
authors: Central Laboratory, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Qiuhui
authors: Q
authors: Pan
authors: Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
authors: Yan
authors: Y
authors: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D001343:Autophagy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009857:Oncogenes; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C469146:guaiol
keywords: (-)-Guaiol; DSBs; RAD51; autophagy; chemosensitivity