ω-hydroxyundec-9-enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines

Joungjwa Ahn, Youn Wook Chung, Jin Byung Park, Kyung Mi Yang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

ω-Hydroxyundec-9-enoic acid (ω-HUA), a plant secondary metabolite, exhibits anti-fungal activity. However, its effect on breast cancer cells is unknown. Here, we investigated the anti- breast cancer activity of ω-HUA and its underlying mechanism. Treatment of human breast cancer cell lines, MDA-MB-231 and MDA-MB-435, with ω-HUA induced apoptotic cell death with increased cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels, and p38 and JNK phosphorylation. Inhibition of these mitogen-activated protein kinase (MAPK) pathways using specific inhibitors or siRNA, for p38 and JNK, respectively, blocked the ω-HUA-induced apoptosis in a dose-dependent manner. Moreover, pretreatment of the cells with antioxidant N-acetyl cysteine (NAC) inhibited ω-HUA-induced increased reactive oxygen species (ROS) levels, cleaved caspase-3 and cleaved PARP, and phosphorylated JNK, phosphorylated p38, and increased cell viability and colony-forming ability. MDA-MB-231 xenograft model showed that the ω-HUA-treated group exhibited greater tumor regression and significantly reduced tumor weight compared to that exhibited by the vehicle-administered group. Collectively, ω-HUA-induced intracellular ROS generation induced breast cancer cell apoptosis through JNK and p38 signaling pathway activation, resulting in tumor regression. The results suggested that ω-HUA is an effective supplement for inhibiting human breast cancer growth.

Original languageEnglish
Pages (from-to)998-1007
Number of pages10
JournalJournal of Cellular Biochemistry
Volume119
Issue number1
DOIs
StatePublished - Jan 2018

Bibliographical note

Funding Information:
This work was supported by the Jungwon University Research Grant (2016-031).

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • anti-cancer effect
  • apoptosis
  • JNK pathway
  • p38 pathway
  • ROS
  • ω-Hydroxyundec-9-enoic acid

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