(-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer

Oncotarget. 2016 Sep 20;7(38):62585-62597. doi: 10.18632/oncotarget.11540.


(-)-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.

Keywords: (-)-Guaiol; DSBs; RAD51; autophagy; chemosensitivity.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma of Lung
  • Animals
  • Antineoplastic Agents / chemistry
  • Apoptosis*
  • Autophagy*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lysosomes / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Oncogenes
  • Rad51 Recombinase / metabolism*
  • Recombination, Genetic
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes, Guaiane


  • Antineoplastic Agents
  • Sesquiterpenes
  • Sesquiterpenes, Guaiane
  • RAD51 protein, human
  • Rad51 Recombinase
  • guaiol