Quercetin has potentially beneficial effects on disease prevention, including cancer. An intriguing issue regarding the mechanisms of action of quercetin is the ability of this drug to modulate estrogen receptor (ER) activities. In a previous study, we demonstrated that quercetin elicited apoptosis through an ERá-dependent mechanism. However, the contribution of ERâ in quercetin-induced apoptosis remains elusive. Here, we report that quercetin, at nutritionally relevant concentrations, mimicked the 17â-estradiol (E2)-induced apoptotic effect in both ERâ1-transfected HeLa and in ERâ1-containing DLD-1 colon cancer cell lines by inducing the activation of p38. p38 activation is responsible for pro-apoptotic activation of caspase-3 and the cleavage of poly(ADP-ribose) polymerase. Notably, no inactivation or downregulation of the survival kinases (i.e., AKT and ERK1/2) or the antiapoptotic protein Bcl-2 was observed after quercetin stimulation. On the contrary, quercetin acted similarly to E2 by increasing the levels of the oncosuppressor protein PTEN and by impeding ERâ-dependent cyclin D1 promoter activity, which subsequently resulted in the transcription of the estrogen-responsive element remaining unchanged. As a whole, these data indicate that quercetin mimics the E2 effects in the presence of ERâ1, thus maintaining its anti-carcinogenic potential. In addition, the quercetin pro-apoptotic action in the presence of ERá may render it as a dual-sided protective agent against E2-related cancer in the reduction of tumour growth in organs that express ERá and/or ERâ.
Antioxidants Apoptosis