Autophagy Induction by Trichodermic Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis in Colon Cancer Cells
| Autor: | Zhenghong Lin, Xu Chen, Xiaolong Yang, Tingting Zou, Junyan Qu, Cheng Zeng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
autophagy
XBP1 QH301-705.5 colorectal cancer Antineoplastic Agents CHOP TDA Catalysis Article Inorganic Chemistry Mice Animals Humans Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Chemistry Endoplasmic reticulum Organic Chemistry ATF4 Autophagy apoptosis General Medicine Endoplasmic Reticulum Stress HCT116 Cells Xenograft Model Antitumor Assays In vitro Computer Science Applications Apoptosis Colonic Neoplasms Unfolded protein response Cancer research ER stress |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 5566, p 5566 (2021) Volume 22 Issue 11 |
| ISSN: | 1422-0067 |
| Popis: | 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 IRE1α/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. |
| Databáze: | OpenAIRE |
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