Dasari Subramanyam, Pathak Nishtha, Thomas Amy, Bitla Shreeja, Kumar Raj, Munirathinam Gnanasekar
School of Medicine, Indiana University Bloomington, Bloomington, IN 47405, USA.
Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL 61108, USA.
Int J Mol Sci. 2023 Sep 18;24(18):14242. doi: 10.3390/ijms241814242.
Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it is crucial to explore novel treatment options that can efficiently target PCa, improve patient survival, and enhance their quality of life. Neferine (Nef), a bioactive compound derived from plants, has emerged as a promising candidate for cancer treatment due to its ability to induce apoptosis, autophagy, and cell cycle arrest. In this study, we investigated the potential anticancer effects of Nef in androgen receptor (AR)-positive LNCaP and VCaP cells, representative models of androgen-dependent PCa. Our findings demonstrate that Nef effectively inhibits cell growth, proliferation, and the tumorigenic potential of androgen-dependent PCa cells. Furthermore, Nef treatment resulted in the excessive production of reactive oxygen species (ROS), leading to the activation of key markers of autophagy and apoptosis. These results suggest that Nef has the potential to target the oncogenic characteristics of androgen-dependent PCa cells by exploiting the potency of ROS and inducing autophagy and apoptosis in AR-positive PCa cells. These findings shed light on the therapeutic potential of Nef as a novel treatment option with reduced side effects for androgen-dependent prostate cancer. Further investigations are warranted to assess its efficacy and safety in preclinical and clinical settings.
去势抵抗在晚期前列腺癌(PCa)的治疗中构成了重大挑战,雄激素剥夺疗法(ADT)或化疗是主要的治疗选择。然而,这些方法往往会导致显著的副作用以及治疗抵抗的产生。因此,探索能够有效靶向PCa、提高患者生存率并改善其生活质量的新型治疗选择至关重要。甲基莲心碱(Nef)是一种从植物中提取的生物活性化合物,由于其能够诱导细胞凋亡、自噬和细胞周期停滞,已成为一种有前景的癌症治疗候选药物。在本研究中,我们研究了Nef在雄激素受体(AR)阳性的LNCaP和VCaP细胞(雄激素依赖性PCa的代表性模型)中的潜在抗癌作用。我们的研究结果表明,Nef能有效抑制雄激素依赖性PCa细胞的生长、增殖和致瘤潜力。此外,Nef处理导致活性氧(ROS)过度产生,进而激活自噬和凋亡的关键标志物。这些结果表明,Nef有可能通过利用ROS的效力并诱导AR阳性PCa细胞中的自噬和凋亡来靶向雄激素依赖性PCa细胞的致癌特性。这些发现揭示了Nef作为一种对雄激素依赖性前列腺癌副作用较小的新型治疗选择的治疗潜力。有必要进行进一步研究以评估其在临床前和临床环境中的疗效和安全性。