# HMT exerts an Anticancer Effect by Targeting PAK-1
## 1 Introduction  
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]. Prostate cancer manifests symptoms such as frequent urination, notcuria, hematuria, erectile dysfunction, and dysuria. Prostate cancer can spread to nearby organs, such as the bladder, or travel through the bloodstream or lymphatic system to bones and other organs [2]. Most prostate cancers require endrogens for growth and are sensitive to androgen deprivation therapy (ADT). However, ADT leads to castration-resistant prostate cancer (CRPC). 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 insurance of prostate cancer cells resistant to testosterone suppression therapy [3]. P21-activated kinase 1 (PAK-1), a member of the serine/threonine kinase family, plays a crucial role in tumor progression and contributes to tumor invasion and metastasis invarious types of human cancer. PAK-1 overexpression occurs in several types of human cancer, including prostate cancer [4; 5]. Moreover, PAK-1 is a major downstream effector of the Rho-family GTPase Cdc42 and Rac1 and is involved in the regulation of cell morphology and motility [6]. Cancer cell migration is a fundamental process in solid tumor formation and is required for metastasis formation [7]. The formation of cancer metastasis, which includes cancer cell migration and invasion, involves changes in cytoskeletal signaling pathways, increased motility, and enhanced cell survival. Thus, the actin cytoskeleton is an important factor in tumor cell migration and invasion [8]. It has been reported that PAK 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]. Furthermore, the expression and activity of LIMK are higher in invasive breast and prostate cancer cell lines than in less invasive lines [14]. In addition, PAK-1 plays an essential role in cell growth, adhesion, migration, and survival in colorectal cancer [15] and lung adenocarcinoma [16], through the activation of AKT, ERK, and \(\beta\)-catenin. The use of complementary and alternative medicine (CAM) treatment methods, including traditional Korean medicine, has shown a steady rise among cancer patients. Many patients seek CAM therapeutic options to mitigate the side effects of chemotherapy and radiation therapy [17; 18]. However, further studies are required to examine the efficacy and safety of CAM in anticancer therapies. Heamatang (HMT) is a traditional medicine that was described in the _Compendium of Materia Medica_ (_Bancao Gangmu_), a Chinese herbological and pharmaceutical textbook written by [PERSON] during the Ming dynasty reign [19]. According to Bancao Gangmu, HMT disperses hard masses caused by accumulation and assemblage of blood clots or waste discharge under deficient and excessive conditions over a long time. Thus, HMT could be applied to cancer treatment. However, there is a lack of scientific evidence regarding its clinical efficacy, as the therapeutic effects of this classic prescription have not been evaluated using conventional scientific methods. HMT is constituted by combining seahorse and six herbal components, namely _Rheum palmatum_, _Pharbitidis mill Choisy_, _Citri unshius Markovich_, _Inula hehium_, _Croton tiglium Lime_, and _Angelica gigas Nakai_. HMT has not been employed in modern medicine because the use of _Hippocamp_ species was prohibited on account of the originating species being endangered. However, we were able to produce HMT in-house thanks to the farming of _Hippocampus abdominalis_ together with its approval for use as food material in Korea.