Curcumin suppresses human papillomavirus oncoproteins, restores p53, rb, and ptpn13 proteins and inhibits benzo[a]pyrene‐induced upregulation of HPV E7

Abstract

Curcumin has great potential as a chemopreventive and chemotherapeutic agent; however, its effects on human papillomavirus (HPV)-associated molecular events are inadequately explored. This study examined the effects of curcumin on HPV-associated pathways involved in developing cervical cancer. We demonstrate for the first time that curcumin treatment suppresses cervical cancer cell growth in a three-dimensional raft culture system. Curcumin also inhibits tumorigenic characteristics as shown by decreases in both clonogenic potential and cell motility. Additionally, our findings show that curcumin treatment inhibits the transcription of HPV16 E6/E7 as early as 6 h posttreatment and restores the expression of tumor suppressor proteins p53, retinoblastoma protein, and PTPN13. While smoking is a recognized risk factor for cervical cancer, the molecular effects of smoke carcinogens on the expression of HPV E6/E7 oncogenes are not well known. We show for the first time that exposure to benzo[a]pyrene (BaP), a tobacco carcinogen, increases the expression of HPV E7 oncoprotein suggesting a molecular link between smoking and cervical cancer. Importantly, curcumin decreases the BaP induced increase in the expression of HPV E7 oncoprotein. The results of this study clearly demonstrate that curcumin alters HPV-associated molecular pathways in cervical cancer cells. These novel findings imply that curcumin may be an effective chemopreventive and therapeutic agent for cervical cancer prevention and treatment.

Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

“…Several preclinical and clinical studies indicated the anticancer potential of curcumin (Basu et al, 2013;Dai et al, 2013;Yin et al, 2013). Curcumin exhibited its antitumor action in HPV associated cervical cancer (Basu et al, 2013) by restoring p53 and pRb (Maher et al, 2011) and by reducing the level of cyclin D1 and activation of tumor suppressor proteins (Singh and Singh, 2011).…”

Synthesis and anticervical cancer activity of novel pH responsive micelles for oral curcumin delivery

“…The CM treatment also activated caspase À3 and À9 as well as downregulated COX-2, iNOS, and cyclin D1 in HeLa, SiHa, and CaSki cell lines (Singh and Singh, 2009). Furthermore, the CM suppressed HPV16 E6/E7 and increased the expression of tumor suppressor proteins p53 and Rb, protein tyrosine phosphatase and non-receptor type 13 (PTPN13), and also inhibited benzopyrene-induced upregulation of HPV E7 in HeLa, SiHa, C33a, and CaSki cervical cancer cell lines (Maher et al, 2011).…”

Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

“…In clinical trials, intravaginally administered Praneem, a polyherbal formulation, was shown to eliminate HPV16 infection in early cervical intraepithelial lesions [71]. Methyl jasmonate, soyasaponin, phytoglycoprotein, curcumin, silymarin, withaferin A, and epigallocatechingallate (EGCG) showed therapeutic effects via repression of viral oncogenes, upregulation of tumor suppressor genes, or induction of apoptosis in vitro [72,73,74,75,76,77,78]. Withaferin A treatment reduced tumor volume by approximately 70% in a xenograft model.…”