Study of Celastrol on Akt Signaling Pathway and Its Roles in the Apoptosis of K562 Cells
Xiaonan Wang, Qing Wu, Xu Yang, Liansheng Zhang, Yiping Wu, Yanwen Shu
DOI: 10.4236/jct.2011.24062   PDF    HTML   XML   4,377 Downloads   7,815 Views   Citations


The purpose Celastrol, the main active compound of the Celastrus genus plants, belonging to Celastraceae, has recently marked antitumour potency on solid tumours of various derivations, Methods: We demonstrate here that Celastrol also present powerful antileukaemic potency through both growth arrest and apoptosis induction in K562 cells, which was accompanied by typical apoptotic morphological and sharp decreased expression of phosphorylation level of Caspase family members and Akt signaling pathway related proteins were determined by western blot before and after celastrol treatment, and further the effect of AKT signaling pathway on celastrol-induced-apoptosis was analyzed. However, in vitro treatment with Celastrol resulted in significantly reduced expression of phophorylation of Akt, Survivin and Bcl-2 significantly in K562 cells. Results: 25 nmol/L WORT (PI3K-Akt inhibitor) can significantly augmented cell apoptosis induced by Celastrol in K562 cells in dose-dependent manner, Moreover, most Caspase3,8,6 were activated in K562 cells during Celastrol treatment, 50 µmol/Lz-VAD-fmk (Caspase inhibitor) can to enhance the apoptosis induced by Celastrol. Discussion: These results suggest that the fact that Akt signaling pathway might act as new targets of Celastrol, correlates well with the sensitivity to Celastrol, as well as the rate of apoptosis induced by Celastrol, Mechanisms that regulate Akt signaling pathway may be provide novel opportunities for drug development.

Share and Cite:

X. Wang, Q. Wu, X. Yang, L. Zhang, Y. Wu and Y. Shu, "Study of Celastrol on Akt Signaling Pathway and Its Roles in the Apoptosis of K562 Cells," Journal of Cancer Therapy, Vol. 2 No. 4, 2011, pp. 463-469. doi: 10.4236/jct.2011.24062.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Yu, M. Rahmani and J. Almenara, “Induction of Apoptosis in Human Leukemia Cells by the Tyrosine Kinase Inhibitor Adaphostin Proceeds through a RAF-1/MEK/ ERK and Akt-Dependent Process,” Oncogene, Vol. 23, No. 7, 2004, pp. 1364-1376. doi:10.1038/sj.onc.1207248
[2] M. Al-Rasheed and P. S. Manogaran, “Curcumin Induces Apoptosis via Inhibition of PI3K-Kinase/Akt Pathway in Acute T Cell Leukemia,” Apoptosis, Vol. 11, No. 2, 2006, pp. 245-254.
[3] A. Salminen, M. Lehtonen and T. Paimela, “Celastrol: Molecular Targets of Thunder God Vine,” Biochemical and Biophysical Research Communications, Vol. 394, No. 3, 2010, pp. 439-442. doi:10.1016/j.bbrc.2010.03.050
[4] D. H. Kim, E. K. Shin and Y. H. Kim, “Suppression of Inflammatory Responses by Celastrol, a Quinone Methide Triterpenoid Isolated from Celastrus Regelii,” European Journal of Clinical Investigation, Vol. 39, No. 9, 2009, pp. 819-827.
[5] Y. Kim, K. Kim and H. Lee, “Celastrol Binds to ERK and Inhibits FcepsilonRI Signaling to Exert an Anti-Effect,” European Journal of Pharmacology, Vol. 612, No. 1-3, 2009, pp. 131-142. doi:10.1016/j.ejphar.2009.03.071
[6] G. Sethi, K. S. Ahn and M. K. Pandey, “Celastrol, a Novel Triterpene, Potentiates TNF-Pinduced Apoptosis and Suoppresses Invasion of Tumor Cells by Inhibiting NF-KappaB Activation,” Blood, Vol. 109, No. 7, 2007, pp. 2727-2735.
[7] D. H. Zhang, A. Marconi and L. M. Xu, “Tripterine Inhibits Expression of Adhesion Molecules Activated Endothelial Cells,” Journal of Leukocyte Biology, 2006, Vol. 80, No. 2, pp. 309-319. doi:10.1189/jlb.1005611
[8] Y. H. Xu and J. Yan, “Effect and Possible Mechanism of Tripterine on Inducing Apoptosis of Human Acute Myelocytic Leukemia HL-60 Cells,” Journal of Zhejiang University (Science Edition), Vol. 35, No. 3, 2008, pp. 311-314.
[9] S. Mukherjee Chakraborty, U. Ghosh and N. P. Bhattacharyya, “Curcumin-Induced Apoptosis in Human Leukemia Cell HL-60 Is Associated with Inhibition of Telomerase Activity,” Molecular and Cellular Biochemistry, Vol. 297, No. 1-2, 2007, pp. 31-39. doi:10.1007/s11010-006-9319-z
[10] H. Yang, D. Chen and Q. C. Cui, “Celastrol, a Triterpene Extracted from the Chinese Thunder of God Vine, Is a Potent Proteasomc Inhibitor and Suppresses Human Prostate Cancer Growth in Nude Mice,” Cancer Research, Vol. 66, No. 9, 2006, pp. 4758-4765.
[11] A. Petronelli, G. Pannitteri and U. Testa, “Triterpenoids as New Promising Anticancer Drugs,” Anticancer Drugs, Vol. 20, No. 10, 2009, pp. 880-892. doi:10.1097/CAD.0b013e328330fd90
[12] J. Wesierska-Gadek, J. Bednarek and Z. M. Kiliańska, “New Face of Antiapoptotic Proteins. II. Survivin,” Postepy Biochemii, Vol. 53, No. 32, 2007, pp. 239-253.
[13] A. Nassar, D. Lawson and G. Cotsonis, “Survivin and Caspase-3 Expression in Breast Cancer: Correlation with Prognostic Parameters, Proliferation, Angiogenesis, and Outcome,” Applied Immunohistochemistry & Molecular Morphology, Vol. 16, No. 2, 2008, pp. 113-120. doi:10.1097/PAI.0b013e318032ea73
[14] R. Zhao, G. A. Follows and P. A. Beer, “Inhibition of the Bcl-xL Deamidation Pathway in Myeloproliferative Disorders,” The New England Journal of Medicine, Vol. 359, No. 26, 2008, pp. 2778-2789. doi:10.1056/NEJMoa0804953

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.