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Hinokitiol induces autophagy in murine breast and colorectal cancer cells
Author(s) -
Wang WeiKuang,
Lin SongTao,
Chang WenWei,
Liu LiWen,
Li Tom YuTung,
Kuo ChunYu,
Hsieh JengLong,
Lee CheHsin
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22023
Subject(s) - autophagy , pi3k/akt/mtor pathway , protein kinase b , programmed cell death , apoptosis , cancer research , microbiology and biotechnology , ribosomal s6 kinase , kinase , signal transduction , p70 s6 kinase 1 , mtorc1 , cell growth , chemistry , biology , biochemistry
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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 77–84, 2016.