前列腺癌 (PCa) 是癌症相关死亡的第二大原因，在美国非裔美国人的死亡率较高。死亡率较高的主要原因是种族差异以及对前列腺癌生物学和负担得起的治疗方法缺乏了解，例如以及非洲裔美国男性获得最有效和安全治疗的经济负担。包括维生素 K 在内的微量营养素对各种癌细胞系的影响已得到广泛研究，但维生素 K3（甲萘醌）类似物 VK3-OCH3 对非裔美国人前列腺癌的潜在抗癌作用尚未得到评估。在这项研究中，我们比较了 VK3-OCH3 对非裔美国人来源的 PCa 细胞系（即 RC77-T 和 MDA-PCa-2b）的抗癌作用。我们的结果表明，VK3-OCH3 显着抑制 RC77-T 和 MDA-PCa-2b 非裔美国人 PCa 细胞的增殖并促进细胞凋亡，并且两种细胞系中细胞死亡的潜在机制似乎相似。值得注意的是，VK3-OCH3 通过阻断非裔美国人 PCa 细胞 G0 期的细胞周期来抑制集落形成能力并诱导细胞凋亡。 VK3-OCH3 还通过抑制非裔美国人 PCa 细胞的转移特性的迁移能力来充当抗转移剂。 VK3-OCH3 介导的非裔美国人 PCa 细胞的细胞死亡与自由基的产生有关，例如细胞内和线粒体活性氧 (ROS)。有趣的是，N-乙酰半胱氨酸 (NAC) 和谷胱甘肽 (GSH) 等抗氧化剂可有效消除 VK3-OCH3 对非裔美国患者 PCa 细胞系诱导的氧化应激。值得注意的是，VK3-OCH3 降低了这些 PCa 细胞中雄激素受体和前列腺特异性抗原的表达。此外，分子动力学研究重申VK3-OCH3与雄激素受体强烈结合，表明雄激素受体是VK3-OCH3的潜在分子靶点。此外，Western blot分析显示，在MDA-PCa-2b转移性PCa细胞模型中，VK3-OCH3可降低雄激素受体、TRX2以及Bcl-2和TCTP等抗凋亡信号分子的表达。总之，我们的结果表明，VK3-OCH3 是一种有前途的抗癌药物，有可能降低非裔美国 PCa 患者的死亡率，值得进一步的临床前和转化研究。© 2024 国际生物化学和分子生物学联合会。

Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.© 2024 International Union of Biochemistry and Molecular Biology.