掘扁枝石松内酯C通过体外诱导氧化应激、细胞凋亡和DNA损伤发挥抗膀胱癌作用。

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro.

作者信息

Yang Che-Wei, Chien Tsu-Ming, Yen Chia-Hung, Wu Wen-Jeng, Sheu Jyh-Horng, Chang Hsueh-Wei

机构信息

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

出版信息

Pharmaceuticals (Basel). 2022 Jul 24;15(8):917. doi: 10.3390/ph15080917.

Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral , and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by -acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.

掘海绵内酯C（EXCC）是一种源自柳珊瑚八放珊瑚的生物活性化合物，其抗癌作用鲜有研究，尤其是对膀胱癌的作用。本研究旨在探讨EXCC对三种膀胱癌细胞（5637、BFTC905和T24）增殖的潜在影响。基于48小时ATP检测，EXCC可抑制膀胱癌细胞增殖。这种抗增殖功能经证实依赖于氧化应激。EXCC上调细胞和线粒体氧化应激，同时消耗谷胱甘肽并降低线粒体膜电位。这些抗增殖和氧化应激事件被N-乙酰半胱氨酸（NAC）抑制，表明EXCC对膀胱癌细胞的抗增殖具有氧化应激调节功能。EXCC上调氧化应激相关反应，如细胞凋亡、半胱天冬酶激活和DNA损伤，而NAC可使其逆转。综上所述，EXCC的抗增殖功能为通过调节氧化应激治疗膀胱癌细胞提供了一种潜在方法。