Involvement of p53-dependent apoptosis signal in antitumor effect of Colchicine on human papilloma virus (HPV)-positive human cervical cancer cells.

Luchun Yan,Chunyan Cao,Ying Zhang,Xinrong Yuan,Zhaohua Yan,Hao Huang,Xiping Luo

doi:10.1042/bsr20194065

Abstract

Colchicine, a plant-derived alkaloid with relatively low toxicity on normal human epidermal keratinocytes (HEKn), has selective inhibitory effect on the growth of CaSki (HPV16-positive) and HeLa (HPV18-positive) human cervical cancer cell lines via the induction of apoptosis. Colchicine (2.5, 5.0 and 10.0 ng/ml) significantly reduced the expression of human papilloma virus (HPV) 16 E6/E7 mRNA and protein in CaSki and HeLa cells. Moreover, reduced expression of E6 and E7 induced by Colchicine resulted in the up-regulation of tumor suppressor proteins, p53 and Rb, as well as down-regulation of phospho Rb (pRb) protein. In addition, Bax, cytosolic cytochrome c and cleaved caspase-3 protein were increased while Bcl-2 protein was decreased significantly by 48 h of Colchicine treatment. These results implied that Colchicine could be explored as a potent candidate agent for the treatment and prevention of HPV-associated cervical cancer without deleterious effects.

Highlights

Cervical cancer is one of the most common malignancies all over the world and ranked the second leading causes of cancer-related death in females [1,2], which is closely related with persistent infection with oncogenic or high-risk (HR) human papilloma virus (HPV)
To determine the cytotoxic effect of Colchicine on cell growth of different HPV cervical cancer cell lines, CaSki (HPV 16 positive), HeLa (HPV 18 positive), C-33A (HPV negative) and normal human epidermal keratinocytes (HEKn) cells exposed to increasing doses of Colchicine for 24, 48 and 72 h, and cell viability was examied by the MTT assay
The results showed that the cell viabilities of CaSki and HeLa were markedly decreased after exposure to Colchicine in dose- and time-responsive manners

Summary

Introduction

Cervical cancer is one of the most common malignancies all over the world and ranked the second leading causes of cancer-related death in females [1,2], which is closely related with persistent infection with oncogenic or high-risk (HR) HPV. More effective and less toxic anti-cancer agents from natural resources have become a research hot topic for cancer prevention and treatment based on their ability to attack multiple molecular targets [9]. These highlight an urgent need for development of efficacious plant-derived virus-specific inhibitors to overcome HPV-associated cervical cancer

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