Gan Xia, Luo Xiaowei, Chen Jingqin, Fang Wenxuan, Nie Mingyi, Lu Humu, Liu Yonghong, Wang Xueni
Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, 530200, China.
Guangxi Key Laboratory of Marine Drugs, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, 530200, China.
Mol Cell Biochem. 2025 Feb;480(2):1089-1104. doi: 10.1007/s11010-024-05026-9. Epub 2024 May 27.
Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.
PI3K/AKT信号通路的异常激活是前列腺癌发生发展的驱动因素。因此，抑制PI3K/AKT信号通路的功能是治疗前列腺癌的一种策略。伊利西考林C是从珊瑚来源的真菌硬皮顶孢霉GXIMD 02501中分离得到的一种阿斯科氯素衍生物，具有抗炎活性，但其对前列腺癌的活性尚未阐明。采用MTT法、平板克隆形成法、流式细胞术和实时细胞分析技术检测伊利西考林C对前列腺癌细胞活力、增殖、凋亡和迁移的影响。利用分子对接软件和表面等离子体共振技术分析伊利西考林C与PI3K/AKT蛋白之间的相互作用。进行蛋白质印迹分析以检测蛋白质表达的变化。最后，使用QikProp软件模拟伊利西考林C在体内的过程，并使用斑马鱼异种移植模型进一步验证伊利西考林C在体内的抗前列腺癌活性。伊利西考林C对前列腺癌细胞具有细胞毒性作用，对PC-33细胞的作用最为显著。伊利西考林C抑制PC-3细胞的增殖和迁移。它还可以阻断PC-3细胞的细胞周期并诱导其凋亡。此外，伊利西考林C可以与PI3K/AKT蛋白结合。此外，伊利西考林C抑制PI3K、AKT和mTOR蛋白的表达，还可以调节PI3K/AKT/mTOR信号通路下游蛋白的表达。此外，计算推测伊利西考林C口服吸收良好，斑马鱼异种移植模型证实了伊利西考林C在体内的抗前列腺癌作用。伊利西考林C是一种有前景的海洋化合物，能够通过对抗PI3K/AKT/mTOR异常激活来诱导前列腺癌细胞凋亡，这表明伊利西考林C可能是抗前列腺癌药物开发的一个可行候选物。这些发现突出了伊利西考林C对抗前列腺癌的潜力，并阐明了其作用机制。
