8-Br-cGMP activates HSPB6 and increases the antineoplastic activity of quinidine in prostate cancer

Abstract

Heat shock protein family B [small] member 6 (HSPB6), widely found in various muscles, has been recently identified as a tumor suppressor gene. However, its role in prostate cancer remains unexplored. Herein, we investigated the expression of HSPB6 in prostate cancer and its association with prognosis. Our findings revealed that HSPB6 downregulation in prostate cancer correlated with a poor prognosis. Moreover, we discovered that HSPB6 can be phosphorylated and activated by 8-Br-cGMP, leading to apoptosis in prostate cancer cells by activating Cofilin. Additionally, we demonstrated that knocking down E2F1 by quinidine administration enhances the transcriptional level of HSPB6. Furthermore, we evaluated the combination of quinidine and 8-Br-cGMP as a potential therapeutic strategy for prostate cancer. Our results revealed that the combined treatment was more effective than either treatment alone in inhibiting the growth of prostate cancer through the HSPB6 pathway, both in vitro and in vivo. Overall, our study provides compelling evidence that HSPB6 suppresses malignant behavior in prostate cancer by inducing apoptosis. The combination of quinidine and 8-Br-cGMP emerges as a promising approach for the treatment of prostate cancer.

Role of actin-binding proteins in prostate cancer

“…Feng et al investigated therapeutic activators and identified 8-Br-cGMP as capable of activating HSPB6 and inducing dephosphorylation of phosphorylated Cofilin, eliciting apoptosis in PCa cells. Notably, the synergistic effect of 8-Br-cGMP and quinidine notably bolstered HSPB6 transcription levels, effectively restraining PCa growth and offering promising prospects for PCa treatment ( Feng et al, 2024 ). Overexpression of miR-608 targets RAC2/PAK4/LIMK1/cofilin, thereby impeding PCa progression (X.…”