Abstract
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 antiaging remedy, treating urinary disorders and increasing energy and vitality. However, the therapeutic applications of this formula have not been evaluated with evidence-based science. 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. 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 and apoptosis-related proteins (increase in c-cas3 and inhibition of PARP and BCL-2). Moreover, HMT suppressed 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. Our findings demonstrated that HMT exerts its anticancer influence through the inhibition of PAK-1. The HMT formula could be applied in various fields, including functional health food and pharmaceutical development.
Highlights
Prostate cancer is the second most frequent malignancy in men worldwide
castrationresistant prostate cancer (CRPC) is advanced prostate cancer that has been known to evolve into either hormone-resistant prostate cancer (HRPC) or androgen-insensitive prostate cancer (AIPC)
The membranes were blocked in 5% nonfat skim milk and probed with primary antibodies for P21-activated kinase 1 (PAK-1) (Abcam, Cambridge, UK), phospho-AKT, AKT, LIMK1/2, phosphoLIMK1/2, cofilin, phospho-cofilin, cyclin D1, PARP, CDK4, CDK6, and cleaved caspase3 (Cell Signaling, Beverly, MA, USA) and β-actin
Summary
Prostate cancer is the second most frequent malignancy in men worldwide. The incidence and mortality rate of prostate cancer worldwide are strongly correlated with aging (over 65 years of age) [1]. CRPC is advanced prostate cancer that has been known to evolve into either hormone-resistant prostate cancer (HRPC) or androgen-insensitive prostate cancer (AIPC) In this type of tumor, intracrine/paracrine androgen production plays a significant role in the insurgence of prostate cancer cells resistant to testosterone suppression therapy [3]. It has been reported that PAKs regulate the actin cytoskeleton during cell motility and invasion [9]. The phosphorylation of both LIMK and cofilin is greatly enhanced in the presence of active PAK [10,11,12,13]. In this study, we evaluated the impact of HMT in prostate cancer therapy using conventional scientific methods
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