Hinokitiol induces autophagy in murine breast and colorectal cancer cells.

Abstract

Hinokitiol is found in the heartwood of cupressaceous plants and possesses several biological activities. Hinokitiol may play an important role in anti-inflammation and antioxidant processes, making it potentially useful in therapies for inflammatory-mediated disease. Previously, the suppression of tumor growth by hinokitiol has been shown to occur through apoptosis. Programmed cell death can also occur through autophagy, but the mechanism of hinokitiol-induced autophagy in tumor cells is poorly defined. We used an autophagy inhibitor (3-methyladenine) to demonstrate that hinokitiol can induce cell death via an autophagic pathway. Further, we suggest that hinokitiol induces autophagy in a dose-dependent manner. Markers of autophagy were increased after tumor cells were treated with hinokitiol. In addition, immunoblotting revealed that the levels of phosphoprotein kinase B (P-AKT), phosphomammalian target of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70S6K) in tumor cells were decreased after hinokitiol treatment. In conclusion, our results indicate that hinokitiol induces the autophagic signaling pathway via downregulation of the AKT/mTOR pathway. Therefore, our findings show that hinokitiol may control tumor growth by inducing autophagic signaling.

• Authors: Wei-Kuang Wang, Song-Tao Lin, Wen-Wei Chang, Li-Wen Liu, Tom Yu-Tung Li, Chun-Yu Kuo, Jeng-Long Hsieh, Che-Hsin Lee
• Journal: Environmental toxicology (Environ Toxicol) Vol. 31 Issue 1 Pg. 77-84 (Jan 2016) ISSN: 1522-7278 [Electronic] United States
• PMID: 25044443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Monoterpenes
• Tropolone
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• beta-thujaplicin

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Female
• Mice
• Monoterpenes (therapeutic use, toxicity)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tropolone (analogs & derivatives, therapeutic use, toxicity)