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

Authors

Vivek Kumar Kashyap, The University of Texas Rio Grande ValleyFollow
Nirnoy Dan
Neeraj Chauhan, The University of Texas Rio Grande ValleyFollow
Qinghai Wang
Saini Setua
Prashanth K. B. Nagesh, The University of Texas Rio Grande Valley
Shabnam Malik, The University of Texas Rio Grande Valley
Vivek Batra
Murali M. Yallapu, The University of Texas Rio Grande ValleyFollow
Duane D. Miller, University of Tennessee Health Science Center
Bilal B. Hafeez, The University of Texas Rio Grande ValleyFollow
Meena Jaggi, The University of Texas Rio Grande ValleyFollow
Subhash C. Chauhan, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

12-3-2019

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<0.05) inhibition of orthotopic xenograft tumor growth in athymic nude mice. Taken together, our results demonstrate the potential anti-cancer efficacy of VERU-111 in in vitro and in vivo. VERU-111 can be explored as a potent therapeutic agent for the treatment of cervical cancer.

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Recommended Citation

Kashyap, V. K., Dan, N., Chauhan, N., Wang, Q., Setua, S., Nagesh, P. K. B., Malik, S., Batra, V., Yallapu, M. M., Miller, D. D., Li, W., Hafeez, B. B., Jaggi, M., & Chauhan, S. C. (2020). VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway. Cancer letters, 470, 64–74. https://doi.org/10.1016/j.canlet.2019.11.035

Publication Title

Cancer letters

DOI

10.1016/j.canlet.2019.11.035

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology