3-Decylcatechol induces autophagy-mediated cell death through the IRE1α/JNK/p62 in hepatocellular carcinoma cells
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Da-Hye Go1,*, Yu Geon Lee1,*, Da-Hye Lee2,3,*, Jin-A Kim1, In-Hwa Jo1, Yeon Soo Han4, Yong Hun Jo4, Kwang-Youn Kim5, Young-Kyo Seo5, Jae-Hak Moon6, Chang Hwa Jung2,3 and Tae-Il Jeon1
1Department of Animal Science, College of Agriculture & Life Science, Chonnam National University, Gwangju, Republic of Korea
2Research Group of Metabolic Mechanism, Korea Food Research Institute, Seongnam, Republic of Korea
3Department of Food Biotechnology, Korea University of Science and Technology, Seongnam, Republic of Korea
4Division of Plant Biotechnology, Institute of Environmentally-Friendly Agriculture (IEFA), College of Agriculture and Life Sciences, Chonnam National University, Gwangju, Republic of Korea
5Department of Integrated Oncological Therapies, IRCCS AOU, San Martino, IST, Largo Rosanna Benzi, Genova, Italy
6Department of Food Science & Technology, Chonnam National University, Gwangju, Republic of Korea
*These authors have contributed equally to this work
Tae-Il Jeon, email: email@example.com
Chang Hwa Jung, email: firstname.lastname@example.org
Keywords: autophagy, cell death, ER stress, hepatocellular carcinoma, urushiol
Received: January 25, 2017 Accepted: April 17, 2017 Published: May 09, 2017
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.
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