Original Research Article
Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a natural compound with influence on proteasome, ER stress and Hsp90
Version of Record online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 2196–2206, May 2012
How to Cite
Wang, W.-B., Feng, L.-X., Yue, Q.-X., Wu, W.-Y., Guan, S.-H., Jiang, B.-H., Yang, M., Liu, X. and Guo, D.-A. (2012), Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a natural compound with influence on proteasome, ER stress and Hsp90. J. Cell. Physiol., 227: 2196–2206. doi: 10.1002/jcp.22956
- Issue online: 23 JAN 2012
- Version of Record online: 23 JAN 2012
- Accepted manuscript online: 22 AUG 2011 09:49AM EST
- Manuscript Accepted: 19 JUL 2011
- Manuscript Received: 31 DEC 2010
- National Science & Technology Major Project ‘Key New Drug Creation and Manufacturing Program’, China. Grant Numbers: 2009ZX09102-122, 2009ZX09304-002, 2009ZX09308-005, 2009ZX09311-001, 2009ZX09502-020
In the present study, we found that celastrol, a natural compound with well-known apoptosis-inducing effect, could also induce paraptosis-like cytoplasmic vacuolization in cancer cell lines including HeLa cells, A549 cells and PC-3 cells derived from cervix, lung and prostate, respectively. Further study using HeLa cells indicated that the vacuoles induced by celastrol might be derived from dilation of endoplasmic reticulum. And, in celastrol-treated cells, markers of autophagy such as transformation of microtubule-associated protein 1 light chain 3 (LC3)I to LC3II and LC3 punctates formation were identified. Interestingly, autophagy inhibitors could not interrupt but enhance the induction of cytoplasmic vacuolization. Furthermore, MAPK pathways were activated by celastrol and inhibitors of MEK and p38 pathways could prevent the formation of cytoplasmic vacuolization. Celastrol treatment also induced G2/M cell cycle arrest and apoptosis in HeLa cells. In conclusion, celastrol induced a kind of paraptosis accompanied by autophagy and apoptosis in cancer cells. The coincidence of apoptosis and autophagy together with paraptosis might contribute to the unique characteristics of paraptosis in celastrol-treated cells such as the dependence of paraptosis on MAPK pathways and dynamic change of LC3 proteins. Both paraptosis and apoptosis could contribute to the cell death induced by celastrol while autophagy might serve as a kind of survival mechanism. The potency of celastrol to induce paraptosis, apoptosis and autophagy at the same dose might be related to its capability to affect a variety of pathways including proteasome, ER stress and Hsp90. J. Cell. Physiol. 227: 2196–2206, 2012. © 2011 Wiley Periodicals, Inc.