title: 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D002211:Capsaicin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen; D002211:Capsaicin