Development of Novel Colchicine Derivative for Anticancer

Due to the deterioration of the environment and food safety, cancer has become a very serious medical problem in recent year. Over 13 million new cases were diagnosed and more than 8 million of people died of cancer-related diseases every year. Most threatening is cancer population has increased steadily. According to the Ministry of Health and Welfare announced “Top ten causes of death in Taiwan”, cancer is ranking the top causes of death over past three decades. Because most types of cancer are highly malignant and poor prognosis, the five years mortality rate is over 80% all over the world. Even worse, the trend of cancer deaths age is getting younger, which arouse the attention of government in Taiwan. Therefore, synthesis and develop new chemotherapy drugs can provide new opportunity for cancer treatment. Microtubules are very important components of the cell which the main functions are to maintain and develop the cytoskeleton, participation vesicular transport and chromosome separation in cell division. Because of its important role in cell division, chemicals can interfere with microtubule dynamic equilibrium will be able to cause damage of microtubules structure thereby impeding the cell mitosis. Therefore microtubule inhibitors have been known to be effectively used in the anticancer. Colchicine, a well-known microtubule inhibitor, can inhibit tumor cell proliferation as well. However, severe toxicity has limited its clinical application which is mainly used in the treatment of acute gout clinically. In this study, a novel colchicine derivative was synthesized and evaluated its anticancer potential through collaboration with Dr Li-xi Yang (California Pacific Medical Center Research Institute, San Francisco, USA). From the preliminary animal study result, toxicity of this novel Colchicine derivative was lower than Colchicine which the lethal dose of Colchicine and this novel Colchicine derivative was 2 mg/kg and 150 mg/kg respectively. Through in vitro study, this compound still retain a high potent anticancer activity in against several types of cancer cell, including hepatocellular carcinoma, breast cancer and esophagus cancer. It implied that this new Colchicine derivative has the potential to develop a new chemotherapy drug.