Capsaicin causes inactivation and degradation of the androgen receptor by inducing the restoration of miR-449a in prostate cancer

Abstract

Capsaicin, a novel antitumor agent extracted from chili peppers, has been proven to induce growth inhibition in various types of cancer including prostate cancer. However, the detailed mechanisms remain largely undiscovered. In the present study, we explored the regulation of the androgen receptor (AR) by capsaicin and further researched the mechanisms of their interaction in AR-positive prostate cancer cells. In the present study, cell viability was assessed by MTT assay. Cell cycle distribution was determined using flow cytometry. Expression levels of cyclin D1, miR-449a, AR and prostate-specific antigen (PSA) were assessed by quantitative real-time polymerase chain reaction or western blot analysis. To further confirm the relationship among miR-449a, AR and prostate cancer proliferation, miR-449a was overexpressed by a lentivirus in prostate cancer cells. We discovered that capsaicin prevented tumor proliferation and cell cycle progression through inactivation and degradation of AR. We also found that restoration of miR-449a induced by capsaicin treatment resulted in the inhibition of AR signaling. Finally, we demonstrated that increased expression of miR-449a sensitized prostate cancer to capsaicin treatment. Finally, our experimental results indicated that capsaicin negatively modulates the activity of AR at the mRNA and protein levels by restoring miR-449a profiling in prostate cancer. In addition, increased expression of miR-449a may facilitate the sensitivity of prostate cancer to capsaicin treatment. Thus, capsaicin may be developed as a novel anti-AR drug for the therapy of prostate cancer.

Anticancer Effects of Nutraceuticals in the Mediterranean Diet: An Epigenetic Diet Model

“…Capsaicin exhibits antiproliferative actions on prostate cancer cells by inducing apoptosis. It reduces the expression of the androgenic receptor, inhibits the activity of the proteasome which suppresses the degradation of inhibitor of nuclear factor kappa B (IĸBα), thereby preventing the activation of NF-ĸB (152). Such actions might play a role in the treatment of prostate cancer, even hormone-independent.…”

An updated review on molecular mechanisms underlying the anticancer effects of capsaicin

“…Capsaicin caused micro-RNA-mediated modulation of cell survival pathways: Recent studies have demonstrated that capsaicin can modulate the expression of certain microRNAs (miR), thereby inducing apoptosis in pancreatic, prostate, and liver cancer cells. Incubation of human prostate cancer cells with capsaicin reduced androgen receptor (AR)-mediated signaling via induction of miR-449a (98). Capsaicin diminished the expression of microRNA miR-520a-5p, and combined treatment with miR-520a-5p inhibitor with capsaicin showed more potent anti-proliferative effects in K562 leukemic cells compared with capsaicin treatment alone (99).…”

Evaluation of the Anti-Proliferative Effects of a Green Tea and <i>Capsicum</i> Powder Extract in Cancer Cell Lines

“…Recently, capsaicin has been evaluated for anti-carcinogenic properties. Capsaicin effects on prostate cancer using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model was found to be chemopreventive [6], whereas it was also found to decrease prostate cancer cell proliferation and cell cycle progression through the inactivation of androgen receptor [7]. It was also found to modulate extracellular matrix components in an experimentally induced lung cancer model, suggesting it could also have an anti-tumor effect in lung cancer as well [8].…”