EHMT2 inhibitor BIX-01294 induces endoplasmic reticulum stress mediated apoptosis and autophagy in diffuse large B-cell lymphoma cells
| Autor: | Kailin Xu, Mingshan Niu, Yuanyuan Qin, Xuguang Song, Pu Yang, Feng Zhu, Yu Tian, Mengdi Liu, Xiaoshen Sun, Lingyu Zeng, Dongmei Yan, Cai Sun, Zhenyu Li, Jun Jiao, Linyan Xu, Xiang Gao, Wei Sang |
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| Rok vydání: | 2021 |
| Předmět: |
autophagy
Cyclin E Chemistry Cell growth Endoplasmic reticulum Autophagy ATF4 apoptosis medicine.disease diffuse large B cell lymphoma BIX-01294 Oncology immune system diseases Apoptosis hemic and lymphatic diseases endoplasmic reticulum stress Cancer research Unfolded protein response medicine Diffuse large B-cell lymphoma Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| DOI: | 10.7150/jca.48310 |
| Popis: | Despite advancement in the treatment of diffuse large B-cell lymphoma (DLBCL), many patients tend to relapse or become refractory after initial therapy. Therefore, it is essential to identify novel therapeutic targets and drugs, understand the molecular pathogenesis mechanism of DLBCL, and find ways to prevent and treat relapsed or refractory DLBCL. BIX-01294 is a small molecule compound that specifically inhibits EHMT2 activity. In this study, we demonstrate that BIX-01294 triggered the inhibition of human DLBCL cell proliferation, lead to G1 phase arrest via increasing P21 level and reducing cyclin E level. BIX-01294 also induced apoptosis via endogenous and exogenous apoptotic pathways. Moreover, BIX-01294 triggered autophagy and activated ER stress in human DLBCL cells. Furthermore, we showed that both key components of ER stress, ATF3, and ATF4, are required for BIX-01294-induced apoptosis and autophagy. Hence, this study provides new evidence that EHMT2 may be a new therapeutic target, and BIX-01294 may be a potential therapeutic drug for treating DLBCL. |
| Databáze: | OpenAIRE |
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