期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms22115566
关键词
TDA; ER stress; apoptosis; autophagy; colorectal cancer
资金
- Natural Science Foundation [cstc2020jcyj-msxmX0154]
- National Natural Science Foundation of China [31571454, 81872755, 82073714]
- Talented Youth Cultivation Program from the Fundamental Research Funds for the Central Universities, South-Central University for Nationalities [CZP20008]
Trichodermic acid (TDA) demonstrates anticancer effects on colorectal cancer cells by inducing endoplasmic reticulum stress and autophagy-mediated apoptosis, suggesting a potential effective strategy for CRC treatment.
Colorectal cancer (CRC) is the third leading malignant tumor in the world, which has high morbidity and mortality. In this study we found that trichodermic acid (TDA), a secondary metabolite isolated from the plant endophytic fungus Penicillium ochrochloronthe with a variety of biological and pharmacological activities, exhibited the antitumor effects on colorectal cancer cells in vitro and in vivo. Our results showed that TDA inhibited the proliferation of colon cancer cells in a dose-dependent manner. TDA induces sustained endoplasmic reticulum stress, which triggers apoptosis through IRE1 alpha/XBP1 and PERK/ATF4/CHOP pathways. In addition, we found that TDA mediated endoplasmic reticulum stress also induces autophagy as a protective mechanism. Moreover, combined treatment of TDA with autophagy inhibitors significantly enhanced its anticancer effect. In conclusion, our results indicated that TDA can induce ER stress and autophagy mediated apoptosis, suggesting that targeting ER stress and autophagy may be an effective strategy for the treatment of CRC.
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