Department of Chinese Medicine and Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Chinese Medicine and Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Mitochondrion. 2014 Jul;17:22-33. doi: 10.1016/j.mito.2014.05.002. Epub 2014 May 14.
Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological characteristics including anti-inflammation, anti-virus, anti-bacteria, anti-hepatotoxicity and anti-cancer. This study provides molecular evidence associated with the dynamics and organization of mitochondria in osteosarcoma 143B cells resulted from P urinaria. Herein, P. urinaria-induced cytotoxicity and ROS associated with the inhibition of mitochondrial membrane potential were reversed by N-acetylcysteine (NAC). The endogenous antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) were activated by P. urinaria, but not correlated to catalase. P. urinaria decreased mitochondrial respiration activity as well as respiratory chain enzymes and HIF-1α in osteosarcoma 143B cells. Additionally, both adenosine triphosphate (ATP) synthase activation and ATP production were suppressed by P. urinaria. We further investigated changes of mitochondrial dynamic in osteosarcoma 143B cells. P. urinaria indeed fragmented the mitochondrial network of osteosarcoma 143B cells. We found a significant decrease in optic atrophy type 1 (Opa1) and mitofusin 1 (Mfn1) related to fusion proteins as well as increase mitochondrial fission 1 protein (Fis1) related to fission protein. It indicated that P. urinaria modulated the mitochondrial dynamics via fusion and fission machinery. Altogether, this study offers the evidence that mitochondrial dysfunction with dynamic change is essential components for the anti-cancer mechanism elicited by P. urinaria.
水飞蓟素（P. urinaria）是一种广泛使用的草药，已被报道具有多种生物学特性，包括抗炎、抗病毒、抗菌、抗肝毒性和抗癌。本研究提供了与水飞蓟素引起的骨肉瘤 143B 细胞中线粒体动态和组织相关的分子证据。在此，N-乙酰半胱氨酸（NAC）逆转了水飞蓟素诱导的细胞毒性和与线粒体膜电位抑制相关的 ROS。内源性抗氧化酶，如锰超氧化物歧化酶（MnSOD）和谷胱甘肽过氧化物酶（GPX1）被水飞蓟素激活，但与过氧化氢酶无关。水飞蓟素降低了骨肉瘤 143B 细胞中的线粒体呼吸活性以及呼吸链酶和 HIF-1α。此外，水飞蓟素还降低了腺嘌呤核苷三磷酸（ATP）合酶的活性和 ATP 的产生。我们进一步研究了骨肉瘤 143B 细胞中线粒体动态的变化。水飞蓟素确实使骨肉瘤 143B 细胞的线粒体网络碎片化。我们发现与融合蛋白相关的视神经萎缩 1 型（Opa1）和线粒体融合蛋白 1（Mfn1）显著减少，而与分裂蛋白相关的线粒体分裂 1 蛋白（Fis1）增加。这表明水飞蓟素通过融合和分裂机制调节线粒体动力学。总之，这项研究提供了证据，表明线粒体功能障碍与动态变化是水飞蓟素抗癌机制的重要组成部分。
