Citrate, a Glycolytic Inhibitor, Inhibits the Growth of Cancer Cells with Highly Glycolytic Activity

• Main Authors: Yi-ShanLi, 李懿珊
• Other Authors: Wen-Tsan Chang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/36623747642913191604

碩士 === 國立成功大學 === 生物化學暨分子生物學研究所 === 101 === Citrate is an organic weak acid exists in vegetables and fruits. It has been used in food industrial, cosmetic science and biomedicine fields, and is a compound of high stability and safety. Citrate also plays an important role in biochemistry, serving as the first deriviative metabolite in tricaboxylic acid cycle, and a modulator in fatty acid synthesis. Particularly, previous studies indicate that citrate is an inhibitor of glycolysis. Malignant tumor cell has an inclination of shifting its metabolic pathway from traditional TCA cycle to glycolytic pathway, a phenomenon called Warburg effect. In our previous research, we found out that a cervical cancer cell line will undergo malignant transformation after persistent silencing of citrate synthase. This cell line has a higher resistance to Etoposide and radiation treatment, but is much more sensitive to glucose deprivation culture enviornment, suggesting that these cells shift its energy consumption pathway to glycolysis metabolism. In this study I use glycolysis inhibitor, sodium citrate, as an anti-tumor drug. My experiment results suggest that sodium citrate can kill this cell line with high efficiency. This result is also confirmed in treating with stable silencing of Lactate dehydrogenase B or Hexokinase I tumor cell line which are also a kind of malignant tumor cell lines. On the contrary, stable silencing of Lactate dehydrogenase A or Hexokinase II tumor cell line, which uses oxidative phosphorylation as its energy source, shows no such drug sensitivity after sodium citrate treatment. This indicates that sodium citrate can specifically kill these malignant tumor cell lines. In spite of the treatment to our own established cell lines, I also treat sodium citrate with other wild type tumor cell lines, and get the same result. My western data shows that glycolytic enzymes Hexokinase II and LDHA have a lower expression pattern after drug treatment. According to other studies, inhibition of these two enzyme expressions would lead to glycolysis pathway shut down and force cells’apoptosis. Sodium citrate and Potassium citrate play different roles clinically, but have shown the same result in the experiment, suggesting that it is the citrate compound, not the metal ions, that inhibits malignant tumor growth. Followed by previous experiments, we also find out the same result in animal experiments. To summarize the experiment results, we suggest that citrate could be a potential anti-tumor drug with a lower price and highly stability. It is also possible that we can treat the patients with different metal ions compounds according to their condition.