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Int J Mol Sci. 2018 Apr 27;19(5). pii: E1309. doi: 10.3390/ijms19051309.

Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells.

Author information

1
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. woosm724@gmail.com.
2
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. ssu3885@gmail.com.
3
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. Kyoungjin.min@gmail.com.
4
Physiology of Department, School of Medicine, Keimyung University, Daegu 42601, Korea. ssim73@kmu.ac.kr.
5
Department of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea. namjo73@gmail.com.
6
Department of Life Science, College of Science and Technology, Daejin University, Kyeonggido 11159, Korea. jchang@daejin.ac.kr.
7
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. god98005@dsmc.or.kr.
8
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. j303nih@dsmc.or.kr.
9
Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Korea. kwontk@dsmc.or.kr.

Abstract

Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor), necroptosis inhibitor (necrostatin-1), or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO)). Furthermore, corosolic acid significantly induces reactive oxygen species (ROS) levels, but antioxidants (N-acetyl-l-cysteine (NAC) and trolox) do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498), breast cancer (MDA-MB231), and hepatocellular carcinoma (SK-Hep1 and Huh7) cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.

KEYWORDS:

corosolic acid; lipid ROS; non-apoptotic cell death; α-tocopherol

PMID:
29702597
PMCID:
PMC5983573
DOI:
10.3390/ijms19051309
[Indexed for MEDLINE]
Free PMC Article

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