College of Medicine, Dankook University, Cheonan-si, Chungcheongnam-do 330-714, Republic of Korea.
Biochem Biophys Res Commun. 2015 Jan 9;456(2):621-5. doi: 10.1016/j.bbrc.2014.12.005. Epub 2014 Dec 8.
Betaine protects cells from environmental stress and serves as a methyl donor in several biochemical pathways. It reduces cardiovascular disease risk and protects liver cells from alcoholic liver damage and nonalcoholic steatohepatitis. Its pretreatment can rescue cells exposed to toxins such as rotenone, chloroform, and LiCl. Furthermore, it has been suggested that betaine can suppress cancer cell growth in vivo and in vitro. Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP. Reduced mitochondrial respiration and energy status have been found in many human pathological conditions including aging, cancer, and neurodegenerative disease. In this study we investigated whether betaine directly targets mitochondria. We show that betaine treatment leads to an upregulation of mitochondrial respiration and cytochrome c oxidase activity in H2.35 cells, the proposed rate limiting enzyme of ETC in vivo. Following treatment, the mitochondrial membrane potential was increased and cellular energy levels were elevated. We propose that the anti-proliferative effects of betaine on cancer cells might be due to enhanced mitochondrial function contributing to a reversal of the Warburg effect.
甜菜碱可保护细胞免受环境压力的影响，并作为几种生化途径中的甲基供体。它可以降低心血管疾病的风险，保护肝细胞免受酒精性肝损伤和非酒精性脂肪性肝炎的损害。其预处理可以挽救暴露于鱼藤酮、氯仿和 LiCl 等毒素的细胞。此外，有人认为甜菜碱可以在体内和体外抑制癌细胞的生长。线粒体电子传递链（ETC）复合物产生线粒体膜电位，这对于产生细胞能量 ATP 至关重要。在包括衰老、癌症和神经退行性疾病在内的许多人类病理条件下，都发现线粒体呼吸和能量状态降低。在这项研究中，我们研究了甜菜碱是否直接靶向线粒体。我们表明，甜菜碱处理可导致 H2.35 细胞中线粒体呼吸和细胞色素 c 氧化酶活性的上调，这是体内 ETC 的拟议限速酶。治疗后，线粒体膜电位增加，细胞能量水平升高。我们提出，甜菜碱对癌细胞的抗增殖作用可能是由于增强的线粒体功能导致沃伯格效应的逆转。
