期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 246, 期 13, 页码 1541-1553出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/15353702211004870
关键词
Hydnocarpin D; T-ALL; apoptosis; ferroptosis; autophagy
资金
- National Natural Science Foundation of China [81703549, 81774003]
- Zhejiang Provincial Natural Science Fund [LQ19H1600060]
- Zhejiang Chinese Medical University Research Fund Project [KC201912, 2018ZZ09]
Hydnocarpin D (HD) inhibits T-ALL proliferation by inducing cell cycle arrest and apoptosis, while also promoting autophagy and ferroptosis. Inhibition of autophagy can alleviate HD-induced apoptosis, indicating that autophagy enhances the efficacy of HD.
Hydnocarpin D (HD) is a bioactive flavonolignan compound that possesses promising anti-tumor activity, although the mechanism is not fully understood. Using T cell acute lymphoblastic leukemia (T-ALL) cell lines Jurkat and Molt-4 as model system, we found that HD suppressed T-ALL proliferation in vitro, via induction of cell cycle arrest and subsequent apoptosis. Furthermore, HD increased the LC3-II levels and the formation of autophagolysosome vacuoles, both of which are markers for autophagy. The inhibition of autophagy by either knockdown of ATG5/7 or pre-treatment of 3-MA partially rescued HD-induced apoptosis, thus suggesting that autophagy enhanced the efficacy of HD. Interestingly, this cytotoxic autophagy triggered ferroptosis, as evidenced by the accumulation of lipid ROS and decrease of GSH and GPX4, while inhibition of autophagy impeded ferroptotic cell death. Our study suggests that HD triggers multiple cell death processes and is an interesting compound that should be evaluated in future preclinical studies.
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