Corosolic acid induces non-apoptotic cell death through generation of lipid reactive oxygen species production in human renal carcinoma caki cells

Seon Min Woo, Seung Un Seo, Kyoung Jin Min, Seung Soon Im, Ju Ock Nam, Jong Soo Chang, Shin Kim, Jong Wook Park, Taeg Kyu Kwon

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish
Article number1309
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • Corosolic acid
  • Lipid ROS
  • Non-apoptotic cell death
  • α-tocopherol

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