Platycodin D targets Hsp90 activity by disrupting Hsp90/Cdc37 cochaperones interaction

UM > Institute of Chinese Medical Sciences

Status	已發表Published
	Platycodin D targets Hsp90 activity by disrupting Hsp90/Cdc37 cochaperones interaction
	Li, T; Wei, B; Chen, X; Chen, X. P.; Ouyang, D.; Yan, R.; Wang, Y. T.; Lu, J.
	2016-12-01
Source Publication	The 5th GuangZhou international symposium oncology, the 1st annual symposium of the Chinese Association of targeted therapy in oncology
Abstract	Objective: Heat shock protein 90 (Hsp90) is a therapeutic target for cancer treatment, and inhibition of Hsp90 will presumably result in suppression of multiple survival signaling pathways. Platycodin D (PD) is a saponin isolated from traditional Chinese medicine Platycodonis Radix with potent anti-cancer activity against a number of cancer. In this study, we intend to identify PD as a novel Hsp90 inhibitor. Methods: Computational molecular docking, Malachite Green Phosphate Assay, Real-time PCR, western blotting and immunoprecipitation were adopted on the research of PD and Hsp90 interaction in NSCLC cells. Results: We found that PD could directly bind to the N-terminal domain of Hsp90, but did not affect ATP binding to Hsp90, which is in contrast to the classical Hsp90 inhibitor 17-AAG. Immunoprecipitation figured out that PD disrupted the Hsp90/cell division cycle protein 37 (Cdc37) cochaperone interaction. This disruption led to the degradation of multiple Hsp90 client proteins via the proteasome pathway without the feedback increase of Hsp70. Conclusion: PD is a novel Hsp90 inhibitor by disrupting protein-protein interaction of Hsp90 and its chaperone Cdc37. These data provide a novel strategy for screening Hsp90 inhibitors from natural products and through disruption of Hsp90-cochaperones interaction.
Keyword	Hsp90 inhibitor platycodin D Cdc37 cochaperones interaction
Language	英語English
The Source to Article	PB_Publication
PUB ID	36500
Document Type	Conference paper
Collection	Institute of Chinese Medical Sciences
Corresponding Author	Lu, J.
Recommended Citation GB/T 7714	Li, T,Wei, B,Chen, X,et al. Platycodin D targets Hsp90 activity by disrupting Hsp90/Cdc37 cochaperones interaction[C], 2016.
APA	Li, T., Wei, B., Chen, X., Chen, X. P.., Ouyang, D.., Yan, R.., Wang, Y. T.., & Lu, J. (2016). Platycodin D targets Hsp90 activity by disrupting Hsp90/Cdc37 cochaperones interaction. The 5th GuangZhou international symposium oncology, the 1st annual symposium of the Chinese Association of targeted therapy in oncology.

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