VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway

Published on Feb 1, 2020in Cancer Letters7.36
· DOI :10.1016/J.CANLET.2019.11.035
Vivek Kumar Kashyap1
Estimated H-index: 1
(UTHSC: University of Tennessee Health Science Center),
Vivek K. Kashyap8
Estimated H-index: 8
(UTHSC: University of Tennessee Health Science Center)
+ 11 AuthorsSubhash C. Chauhan5
Estimated H-index: 5
(UTHSC: University of Tennessee Health Science Center)
Sources
Abstract
Abstract In this study, we investigated the therapeutic efficacy of VERU-111 in vitro and in vivo model systems of cervical cancer. VERU-111 treatment inhibited cell proliferation and, clonogenic potential, induce accumulation of p53 and down regulated the expression of HPV E6/E7 expression in cervical cancer cells. In addition, VERU-111 treatment also decreased the expression of phosphorylation of Jak2 (TyR1007/1008) and STAT3 at Tyr705 and Ser727. VERU-111 treatment arrested cell cycle in the G2/M phase and modulated cell cycle regulatory proteins (cyclin B1, p21 p34cdc2 and pcdk1). Moreover, VERU-111 treatment induced apoptosis and modulated the expression of Bid, Bcl-xl, Survivin, Bax, Bcl2 and cleavage in PARP. In functional assays, VERU-111 markedly reduced the tumorigenic, migratory, and invasive potential of cervical cancer cells via modulations of MMPs. VERU-111 treatment also showed significant (P
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