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Oncotarget. 2017 May 9;8(35):58790-58800. doi: 10.18632/oncotarget.17732. eCollection 2017 Aug 29.

3-Decylcatechol induces autophagy-mediated cell death through the IRE1α/JNK/p62 in hepatocellular carcinoma cells.

Author information

1
Department of Animal Science, College of Agriculture & Life Science, Chonnam National University, Gwangju, Republic of Korea.
2
Research Group of Metabolic Mechanism, Korea Food Research Institute, Seongnam, Republic of Korea.
3
Department of Food Biotechnology, Korea University of Science and Technology, Seongnam, Republic of Korea.
4
Division of Plant Biotechnology, Institute of Environmentally-Friendly Agriculture (IEFA), College of Agriculture and Life Sciences, Chonnam National University, Gwangju, Republic of Korea.
5
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
6
Department of Food Science & Technology, Chonnam National University, Gwangju, Republic of Korea.
#
Contributed equally

Abstract

The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation. The autophagy inhibitor, chloroquine, suppressed autolysosome formation and cell death induction by DC, indicating an autophagic cell death. Interestingly, DC also activated the endoplasmic reticulum (ER) stress response that promotes autophagy via p62 transcriptional activation involving the inositol-requiring enzyme 1α/c-Jun N-terminal kinase/c-jun pathway. We also show that cytosolic calcium mobilization is necessary for the ER stress response and autophagy induction by DC. These findings reveal a novel mechanism by which this urushiol derivative induces autophagic cell death in HCC.

KEYWORDS:

ER stress; autophagy; cell death; hepatocellular carcinoma; urushiol

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