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Abstract Title:

Celastrol induce apoptosis of human multiple myeloma cells involving inhibition of proteasome activity.

Abstract Source:

Eur J Pharmacol. 2019 Jun 15 ;853:184-192. Epub 2019 Mar 27. PMID: 30928629

Abstract Author(s):

Yue-Ling Zhong, Gao-Jie Xu, Sheng Huang, Li Zhao, Yan Zeng, Xiao-Fan Xiao, Jing-Lin An, Jin Liu, Tai Yang

Article Affiliation:

Yue-Ling Zhong

Abstract:

Celastrol exhibits anticancer activity and has a number of potential molecular targets. Among them, the proteasome has attracted particular attention. Although celastrol inhibits multiple myeloma (MM) cell proliferation, the induction of proteasome-inhibitory activity by celastrol in MM cells at the cellular level and in tumors of mice bearing xenografts has not been confirmed. In the present study, we found that celastrol inhibited the caspase-like (β1), trypsin-like (β2) and chymotrypsin-like (β5) proteasome activities of purified human 20S proteasomes, with half-maximal inhibitory concentration (IC50) values of 7.1, 6.3, and 9.3 μmol/L, respectively. Celastrol also inhibited human MM cellular β1, β2, and β5 proteasome activities, with IC50 values of 2.3, 2.1, and 0.9 μmol/L, respectively. After MM cells were treated with celastrol, a population of apoptotic cells and a population of cells in G0/G1 were observed. Celastrol also inhibited proteasome activity and induced apoptosis in tumor tissue. Treatment of MM.1S and RPMI 8226 tumor-bearing severe combined immunodeficiency (SCID) mice with celastrol reduced the tumor volume. In conclusion, our results reveal the effects of celastrol on proteasome activity in MM cells and shed light on the underlying mechanisms of its anticancer activity, providing a basis for developing celastrol as a potential therapeutic agent for MM.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Apoptotic : CK(5217) : AC(3846)

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