4.2 Article

A trienone analog of curcumin, 1,7-bis(3-hydroxyphenyl)-1,4,6-heptatrien-3-one, possesses ROS- and caspase-mediated apoptosis in human oral squamous cell carcinoma cells in vitro

期刊

APPLIED BIOLOGICAL CHEMISTRY
卷 63, 期 1, 页码 -

出版社

SPRINGER SINGAPORE PTE LTD
DOI: 10.1186/s13765-020-0491-8

关键词

Trienone; Curcumin analog; Cytotoxicity; Human mouth squamous cell carcinoma cells; Reactive oxygen species; Apoptosis

资金

  1. Faculty of Science and Technology Research Fund, Prince of Songkla University, Pattani Campus [SAT610461S]
  2. Thailand Research Fund [DBG6180030]

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The leading causes of oral cancer treatment failure are cancer metastasis and chemotherapeutic resistance. Thus, developing novel anticancer agents that are effective against those aggressive cancer cells would be important for complementary or alternative treatments. The objective of this study was to investigate cytotoxicity and anticancer mechanisms of a synthetic trienone analog of curcumin, 1,7-bis(3-hydroxyphenyl)-1,4,6-heptatrien-3-one (trienone 11), against human oral squamous cell carcinoma (OSCC) cells exhibiting multidrug resistance (CLS-354/DX). The study of cytotoxicity showed that trienone 11 exerted threefold stronger cytotoxicity to CLS-354/DX cells than curcumin. Trienone 11 (15-30 mu M) markedly induced intracellular reactive oxygen species (ROS) resulting in apoptotic cell death within 24 h, through activation of caspase-3/7 and caspase-9. A ROS inhibitor, N-acetylcysteine (NAC) prevented apoptotic cell death via decreasing caspase activation. Thus, the cytotoxicity of trienone 11 against CLS-354/DX cells was ROS-mediated intrinsic apoptosis. Overall, trienone 11 could be an interesting lead for developing anti-cancer agents against multidrug resistant OSCC cells.

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