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(-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer.
- Source :
-
Oncotarget [Oncotarget] 2016 Sep 20; Vol. 7 (38), pp. 62585-62597. - Publication Year :
- 2016
-
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.<br />Competing Interests: All the authors in the study declare no potential conflicts of interest.
- Subjects :
- Adenocarcinoma drug therapy
Adenocarcinoma of Lung
Animals
Antineoplastic Agents chemistry
Carcinoma, Non-Small-Cell Lung drug therapy
Cell Line, Tumor
DNA Breaks, Double-Stranded
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms drug therapy
Lysosomes metabolism
Male
Mice
Mice, Nude
Neoplasm Transplantation
Oncogenes
Recombination, Genetic
Sesquiterpenes, Guaiane
Adenocarcinoma metabolism
Apoptosis
Autophagy
Carcinoma, Non-Small-Cell Lung metabolism
Lung Neoplasms metabolism
Rad51 Recombinase metabolism
Sesquiterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27566579
- Full Text :
- https://doi.org/10.18632/oncotarget.11540