Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition

Cheng Chin Chung, Tung Yung Huang, Hung Ru Chu, Roberto De Luca, Elena Candelotti, Chi Hung Huang, Yu Chen S.H. Yang, Sandra Incerpi, Jens Z. Pedersen, Chi Yu Lin, Haw Ming Huang, Sheng Yang Lee, Zi Lin Li, Chun A. ChangOu, Wen Shan Li, Paul J. Davis, Hung Yun Lin, Jacqueline Whang-Peng, Kuan Wang

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摘要

The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

原文英語
文章編號112850
期刊Food and Chemical Toxicology
161
DOIs
出版狀態已發佈 - 3月 2022

ASJC Scopus subject areas

  • 食品科學
  • 毒理學

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