Minnelide, a prodrug, inhibits cervical cancer growth by blocking HPV-induced changes in p53 and pRb

xlomafota13 shared this article with you from Inoreader Minnelide, a prodrug, inhibits cervical cancer growth by blocking HPV-induced changes in p53 and pRb Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2202-2214. eCollection 2021. ABSTRACT HPV-induced cervical cancer is one of the prevalent gynecological cancers world-wide. In the present study, we determined the efficacy of Minnelide, a prodrug which is converted to its active form (Triptolide) in vivo against cervical cancer cells. Our studies show that Triptolide inhibited HPV-16 and HPV-18 positive cells at nanomolar concentrations. Tumor cells treated with Triptolide failed to grow in 3-D cultures in a concentration-dependent manner. Triptolide markedly reduced E6 and E7 transcript levels. Further studies revealed that exposure to Triptolide increased the levels of p53 and pRb. As a consequence, Caspase-3/7 activation and apoptosis was induced in cervical cancer cells by Triptolide. Subsequently, we evaluated the efficacy of Minnelide in xenotransplantation models of cervical cancer. Minnelide at very low doses effectively inhibited the growth of established cervical cancers in all the three animal models tested. Furthermore, Minnelide treatment was more effective when combined with platinum-based chemotherapy. These studies show that Minnelide can be used to inhibit the growth of cervical cancer. PMID:34094678 | PMC:PMC8167699 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.