Graduate Institute of Cell Biology, College of Life Sciences, China Medical University, Taichung 40402, Taiwan.
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan.
Int J Mol Sci. 2024 Jul 18;25(14):7857. doi: 10.3390/ijms25147857.
Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (PCa). However, prolonged ADT inevitably results in therapy resistance with the emergence of the castration-resistant PCa phenotype (CRPC). Hence, there is an urgent need to explore new treatment options capable of delaying PCa progression. Hispidin (HPD) is a natural polyketide primarily derived from plants and fungi. HPD has been shown to have a diverse pharmacological profile, exhibiting anti-inflammatory, antiviral, cardiovascular and neuro-protective activities. However, there is currently no research regarding its properties in the context of PCa treatment. This research article seeks to evaluate the anti-cancer effect of HPD and determine the underlying molecular basis in both androgen-sensitive PCa and CRPC cells. Cell growth, migration, and invasion assays were performed via the MTS method, a wound healing assay and the transwell method. To investigate if HPD affected the expression of proteins, Western blot analysis was conducted. Furthermore, apoptosis was assessed by Annexin V-FITC/PI staining and Western blot analyses. HPD exhibited a favorable pharmaceutical profile to inhibit cell growth; disrupt the cell cycle; attenuate wound healing, migration and invasion; and induce apoptosis in PCa cells in vitro. The mechanistic results demonstrated that HPD reduced AR, MMP-2 and MMP-9 expression and activated the caspase-related pathway, leading to programmed cell death in PCa cells. We showed the anti-cancer effect of HPD on PCa cells and confirmed its feasibility as a novel therapeutic agent. This study provides significant insights into the delineation of the molecular mechanism of HPD in PCa cells and the development of an effective and safe therapy using HPD to eliminate PCa progression.
雄激素剥夺疗法（ADT）是治疗晚期前列腺癌（PCa）的主要方法。然而，长期的 ADT 不可避免地会导致治疗耐药，出现去势抵抗性前列腺癌表型（CRPC）。因此，迫切需要探索新的治疗方法，以延缓 PCa 的进展。卷曲霉素（HPD）是一种主要来源于植物和真菌的天然聚酮化合物。HPD 具有多种药理学特性，具有抗炎、抗病毒、心血管和神经保护活性。然而，目前尚无关于其在 PCa 治疗中的特性的研究。本研究旨在评估 HPD 的抗癌作用，并确定其在雄激素敏感型 PCa 和 CRPC 细胞中的潜在分子基础。通过 MTS 法、划痕愈合实验和 Transwell 法进行细胞生长、迁移和侵袭实验。为了研究 HPD 是否影响蛋白表达，进行了 Western blot 分析。此外，通过 Annexin V-FITC/PI 染色和 Western blot 分析评估细胞凋亡。HPD 具有抑制细胞生长、破坏细胞周期、减弱伤口愈合、迁移和侵袭以及诱导 PCa 细胞凋亡的良好药物特性。机制研究表明，HPD 降低了 AR、MMP-2 和 MMP-9 的表达并激活了 caspase 相关途径，导致 PCa 细胞程序性死亡。我们展示了 HPD 对 PCa 细胞的抗癌作用，并证实了其作为新型治疗剂的可行性。本研究为阐明 HPD 在 PCa 细胞中的分子机制以及利用 HPD 开发有效和安全的疗法来消除 PCa 进展提供了重要见解。
