Hydroxychloroquine Blocks Autophagy and Promotes Apoptosis of the Prostate after Castration in Rats

Abstract

Autophagy is an important pro-survival mechanism and closely related to apoptosis. The aim of this study was to investigate whether hydroxychloroquine (HCQ) blocks autophagy and promotes apoptosis of the prostate after castration. Methods: Thirty-six male SD rats were randomly divided into 3 groups (n = 12): control group (sham operation), castration group, and HCQ group (castrated and treated with HCQ). On day 7, all mice were executed and prostates were isolated. The morphological changes of prostates were observed by light microscope, and the ultrastructure changes were observed under scanning electron microscope (SEM). The protein expression of Beclin-l, P62, caspase-3, Bcl-2, and Bax was assessed by immunohistochemical analyses. The mRNA expression of microtubule-associated protein light chain 3 (LC3) and autophagy-related gene 5 (Atg5) was detected by RT-PCR. Results: Prostates of castration group shrank remarkably and prostates of HCQ group shrank more remarkably than castration group. Cytolysosomes were vis

Hydroxychloroquine Modulates m6A RNA Methylation in Prostate Cancer Cells

“…The modulation of reactive oxygen species was suggested as a potential mechanism for the increased cytotoxicity due to autophagy inhibition [20]. In an in vivo study, researchers have shown that HCQ also inhibits autophagy in castration-resistant prostate cancer cells and stated that cellular apoptosis is induced as a result of inhibition [21]. Numerous investigations have delved into the potential applications of HCQ in the realm of cancer, with a particular emphasis on its connection to the intricate autophagy process.…”

“…The combination of HCQ with other agents could increase the cytotoxicity in cancer cells [20]. Autophagy levels rise due to castration resistance, but HCQ treatment has been found to reduce it [21]. Numerous clinical studies have been conducted and continue to explore the effects of using HCQ alone or in combination with other anticancer agents in various types of cancer [22][23][24][25] The significance of m6A in prostate cancer and the highly effective nature of HCQ in this cancer type underscore the need for a study that delves into the connection between these two factors.…”