HMT Inhibits Prostate Cancer Progression by Targeting PAK-1.

Abstract

Background: Heamatang (HMT) is a classic medicinal formula used in traditional Chinese and Korean medicine; it contains seven distinct components, mainly of herbal origin. HMT is used as an anti-aging remedy, in the treatment of urinary disorders, and to increase energy and vitality. However, the therapeutic applications of this formula have not been evaluated with evidence-based science. Methods: Therefore, we assessed HMT through various in vitro methods, including cell viability assay, fluorescence-activated cell sorting assay (FACS), western blotting, migration assay, three-dimensional (3D) cell culture, siRNA-mediated PAK-1 knockdown, and crystal violet assays. Results: HMT decreased PAK-1 expression in PC-3 cells and inhibited cell viability, growth, and motility. The inhibition of cell motility by HMT was correlated with PAK-1-mediated inhibition of Lim domain kinase (LIMK) and cofilin. HMT induced G1 arrest and apoptosis through the transcriptional regulation of cell cycle regulatory proteins (inhibition of cyclin-dependent kinase (CDK) 4, 6, and cyclin D1) and apoptosis-related proteins (increase in cleaved caspase-3 (c-cas3) and inhibition of poly ADP-ribose polymerase (PARP) and B-cell lymphoma 2 (BCL-2)). Moreover, HMT suppressed P21-activated kinase (PAK-1) expression, leading to the inhibition of AKT activities. Finally, we showed that Decursin was the active ingredient involved in the inhibitory effect of HMT on PAK-1. Conclusion: Our findings demonstrated that HMT exerts its anticancer influence through the inhibition of PAK-1 expression. The HMT formula could be applied in various fields, including functional health food and pharmaceutical development.