Irisin Induces Apoptosis in Metastatic Prostate Cancer Cells and Inhibits Tumor Growth In Vivo

SIMPLE SUMMARY: Prostate cancer is the second most common cancer in males worldwide, with αVβ5 integrin being highly expressed in advanced prostate cancer. Irisin, a hormone secreted from skeletal muscles, has been found to reduce the viability and migration of rapidly dividing cells and may have an inhibitory effect on αVβ5. In vitro evaluations showed that irisin reduced PC-3 cell viability to 70%, increased Annexin-V/7AAD positive cell population, altered the expression of apoptotic proteins, and inhibited tumor growth in vivo. This finding can serve as a foundation for further evaluation of irisin’s role in prostate cancer. ABSTRACT: Background: Prostate cancer is the second most common cancer in males worldwide, with αVβ5 in-tegrin, a coactivator receptor, being highly expressed in advanced prostate cancer. Irisin, a hormone secreted from skeletal muscles, can reduce cell viability and migration and potentially inhibit αVβ5. Objective: This study investigates the potential impact of irisin on prostate cancer cells and its underlying mechanism. Methods: In vitro evaluation of the antiproliferative action of irisin on metastatic prostate cancer (PC-3) cells was tested through MTT assay, flow cytometry, and Western blot. An in vivo evaluation of the antiproliferative effect on prostate cancer xenograft was evaluated in nude mice. Results: In vitro evaluations showed that irisin reduced PC-3 cell viability to 70% and increased the Annexin-V/7AAD positive cell population. Irisin altered the expression of apoptotic proteins, αVβ5, and proteins involved in the P13k-Akt pathway. In vivo, irisin inhibited tumor growth and progression, positively affecting animal well-being. In conclusion, irisin has an apoptotic effect on PC-3, possibly through altering αVβ5 and the Bcl2/BAX and P13k-Akt signaling pathway, inhibiting tumor growth in vivo. Conclusion: Our findings can serve as a foundation for further evaluation of irisin’s role in prostate cancer.