Apoptosis induction and inhibition of HeLa cell proliferation by alpha-naphthoflavone and resveratrol are aryl hydrocarbon receptor-independent

Human papilloma viruses 16 and 18 express E6 and E7 oncoproteins. E6 activates and redirects E6-associated protein (E6AP), an E3 ubiquitin ligase. E6AP interacts with Ube2l3, an E2 ubiquitin conjugating enzyme protein (also known as UbcH7), to promote p53 ubiquitination and degradation by the 26S proteasome. Therefore, blocking E6-mediated p53 degradation might be an alternative treatment for cervical cancer. In addition, activation of the aryl hydrocarbon receptor (AHR) induces Ube2l3 expression, resulting in p53 ubiquitination and degradation. The aim of the present study was to determine whether inhibition of AHR in HeLa cells resulted in an increase in p53 and apoptosis along with a decrease in cell proliferation. The results demonstrate that two AHR antagonists, α-naphthoflavone (α-NF) and resveratrol, decreased cell proliferation, arrested cells in the gap 1/synthesis (G1/S) phases, and increased p53 levels and apoptosis. However, knocking out the Ahr gene did not abrogate the effects of α-NF and resveratrol. Moreover, Ahr-null cells presented similar cell proliferation rates and apoptosis levels when compared to control HeLa cells. Taken together, the results indicate that α-NF's and resveratrol's cytostatic and cytotoxic actions, respectively, occur through an AHR-independent mechanism, and that AHR is not required for HeLa cell proliferation.