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Open AccessFeature PaperArticle

Tannic Acid Promotes TRAIL-Induced Extrinsic Apoptosis by Regulating Mitochondrial ROS in Human Embryonic Carcinoma Cells

1
Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea
2
Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Korea
3
Department of Surgery, School of Medicine, Konkuk University, Seoul 05029, Korea
4
Department of Immunology, Hokkaido University Graduate School of Medicine, Sapporo 060-0808, Japan
5
Jilin Green food Engineering Research Institute, Changchun 130000, Jilin, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(2), 282; https://doi.org/10.3390/cells9020282
Received: 27 December 2019 / Revised: 17 January 2020 / Accepted: 22 January 2020 / Published: 23 January 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Breast Cancer)
Human embryonic carcinoma (EC; NCCIT) cells have self-renewal ability and pluripotency. Cancer stem cell markers are highly expressed in NCCIT cells, imparting them with the pluripotent nature to differentiate into other cancer types, including breast cancer. As one of the main cancer stem cell pathways, Wnt/β-catenin is also overexpressed in NCCIT cells. Thus, inhibition of these pathways defines the ability of a drug to target cancer stem cells. Tannic acid (TA) is a natural polyphenol present in foods, fruits, and vegetables that has anti-cancer activity. Through Western blotting and PCR, we demonstrate that TA inhibits cancer stem cell markers and the Wnt/β-catenin signaling pathway in NCCIT cells and through a fluorescence-activated cell sorting analysis we demonstrated that TA induces sub-G1 cell cycle arrest and apoptosis. The mechanism underlying this is the induction of mitochondrial reactive oxygen species (ROS) (mROS), which then induce the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated extrinsic apoptosis pathway instead of intrinsic mitochondrial apoptosis pathway. Moreover, ribonucleic acid sequencing data with TA in NCCIT cells show an elevation in TRAIL-induced extrinsic apoptosis, which we confirm by Western blotting and real-time PCR. The induction of human TRAIL also proves that TA can induce extrinsic apoptosis in NCCIT cells by regulating mROS. View Full-Text
Keywords: Tannic acid; Wnt/β-catenin; mitochondrial ROS; TRAIL; extrinsic apoptosis pathway Tannic acid; Wnt/β-catenin; mitochondrial ROS; TRAIL; extrinsic apoptosis pathway
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Sp, N.; Kang, D.Y.; Jo, E.S.; Rugamba, A.; Kim, W.S.; Park, Y.-M.; Hwang, D.-Y.; Yoo, J.-S.; Liu, Q.; Jang, K.-J.; Yang, Y.M. Tannic Acid Promotes TRAIL-Induced Extrinsic Apoptosis by Regulating Mitochondrial ROS in Human Embryonic Carcinoma Cells. Cells 2020, 9, 282.

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