Phytochemical Synergies in BK002: Advanced Molecular Docking Insights for Targeted Prostate Cancer Therapy

Moon Nyeo Park ¹ Jinwon Choi ¹ Md Maharub ¹ Estéfani Alves ² Fahrul Nurkolis ³ Rosy Iara Maciel De Azambuja Ribeiro ² Han Na Kang ⁴ Sojin Kang ¹ Rony Abdi Syahputra ³ Bonglee Kim ^1*

• ¹ Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Seoul, Republic of Korea
• ² Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
• ³ Sunan Kalijaga State Islamic University Yogyakarta, Yogyakarta, Special Region of Yogyakarta, Indonesia
• ⁴ KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea

Achyranthes japonica (Miq.) Nakai (AJN) and Melandrium firmum (Siebold & Zucc.) Rohrb.(MFR) are medicinal plants recognized for their bioactive phytochemicals, including ecdysteroids, anthraquinones, and flavonoids. This study investigates the anticancer properties of key constituents of these plants, focusing on the BK002 formulation, a novel combination of AJN and MFR. Specifically, the research employs advanced molecular docking and in silico analyses to assess the interactions of bioactive compounds ecdysterone, inokosterone, and 20-hydroxyecdysone (20-HE) with key prostate cancer-related network proteins, including 5α-reductase, CYP17, DNMT1, Dicer, PD-1, and PD-L1. Molecular docking techniques were applied to evaluate the binding affinities contributions of the bioactive compounds in BK002 against prostate cancer-hub network targets. The primary focus was on enzymes like 5α-reductase and CYP17, which are central to androgen biosynthesis, as well as on cancerrelated proteins such as DNA methyltransferase 1 (DNMT1), Dicer, programmed death-1 (PD-1), and programmed death ligand-1 (PD-L1). Based on data from prostate cancer patients, key target networks were identified, followed by in silico analysis of the primary bioactive components of BK002.In silico assessments were conducted to evaluate the safety profiles of these compounds, providing insights into their therapeutic potential. The docking studies revealed that ecdysterone, inokosterone, and 20hydroxyecdysonec demonstrated strong binding affinities to the critical prostate cancer-related enzymes 5α-reductase and CYP17, contributing to a potential reduction in androgenic activity. These compounds also exhibited significant inhibitory interactions with DNMT1, Dicer, PD-1, and PD-L1, suggesting a capacity to interfere with key oncogenic and immune evasion pathways. Ecdysterone, inokosterone, and 20-hydroxyecdysone have demonstrated the ability to target key oncogenic pathways, and their favorable binding affinity profiles further underscore their potential as novel therapeutic agents for prostate cancer. These findings provide a strong rationale for further preclinical and clinical investigations, supporting the integration of BK002 into therapeutic regimens aimed at modulating tumor progression and immune responses.