Abstract:
Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Hence, a possible approach to p53 reactivation and induction of apoptosis in cervical cancer cells is the use of small molecules suppressing the
proteasome function. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger
(Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against several different cancers. In this study we examined the activity of 6G on human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to (i) inhibit chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of
p21cip1/waf1, (iv) cause ROS generation, DNA damage and G2/M cell cycle arrest (v) alter expression levels of p53-mediated apoptotic markers like Bcl2, Bax, cleaved caspase-3 and PARP and (vi) potentiate
the cytotoxicity of cisplatin. In vivo, 6G resulted in significant reduction of tumor volume and weight with a similar trend in the modulation of molecular markers as in vitro. Taken together, our data underscores utility of 6G as a potent therapeutic agent for the treatment and prevention of cervical cancer.
