Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis
Authors Sun L, Yang S, Chi G, Jin X
Received 25 December 2017
Accepted for publication 7 February 2018
Published 20 March 2018 Volume 2018:11 Pages 1583—1593
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Ingrid Espinoza
Libo Sun,1 Shoujun Yang,2 Guonan Chi,1 Xingyi Jin1
1First Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changhun, Jilin, People’s Republic of China; 2Department of Rehabilitation, China-Japan Union Hospital of Jilin University, Changhun, Jilin, People’s Republic of China
Background: Glioblastoma is one of the most aggressive and common malignancies of the central nervous system in humans. Owing to the correlation of high Hsp90 expression with prognosis and clinical pathology features of diverse types of cancer, targeting Hsp90 with small-molecule inhibitors has become a promising anticancer strategy.
Purpose: In this study, we aimed to explore the possibility of anticancer effect of NMS-E973 in giloblastoma and elucidate the mechanism.
Methods: Cell based MTT assay and colony formation assay were used to detect cell viability. Apoptosis was analyzed by nuclear staining with Hoechst 33258 and Annexin V/propidium iodide staining followed by flow cytometry. Western-blot and RT-PCR were used to detect gene expression. Xenograft assay was used to explore the anticancer effect of NMS-E973 in vivo.
Results: We found that NMS-E973 induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS-E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing apoptosis in glioblastoma cells. Furthermore, PUMA was induced by NMS-E973 treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the antitumor effects of NMS-E973.
Conclusion: Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses of NMS-E973. Induction of PUMA might be a potential biomarker for predicting NMS-E973 responses.
Keywords: NMS-E973, PUMA, glioblastoma, apoptosis
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