Studies of the antitumor Effects of Loratadine on Human Colon Carcinoma

• Main Authors: Wei-Ling Tso, 鄒瑋玲
• Other Authors: Wen-Sen Lee
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/26067967751022474281

碩士 === 臺北醫學大學 === 醫學研究所 === 92 === In the present study, we have demonstrated the molecular mechanisms of antitumor effects of Loratadine (LOR) on human colon adenocarcinoma cells (COLO205). LOR is considered to be a long-acting antihistamine with selective peripheral histamine H1-receptor agonistic activity which has been used to relieve allergic rhinitis (seasonal allergy) symptoms, including sneezing, runny nose, itching, and watery eyes. There were none have previously been shown that LOR can inhibit the growth of human Carcinoma. Here, we provide evidence that LOR has antitumor effect on human colon cancer cell line (COLO205). After 24 hours of treatment with dose-dependent LOR, evidence for induction of apoptosis (25 uM )and cell cycle G2/M arrest (50 uM ) were clearly documented by several assays including flow cytometry cell cycle analysis, DNA laddering. The levels of apoptosis and cell cycle regulatory protein were determined by Western blot analysis. Treatment of 25 uM LOR induced apoptosis by activation of caspase 8, caspase 3, bid, caspase 9, and PARP. Moreover, cytochrome C was released from mitochondria into the cytoplasm, and AIF was translocated from mitochondria to the nucleus. Clearly, LOR-induced cell apoptosis involved in both death receptor and mitochondria pathway. By 50 uM LOR inducing cell cycle G2/M arrest, the protein levels of p53 and p21Cip1 were significantly elevated, but the expression of CDK2、cyclinA2、cdc2、cyclinB were decreased as well as the inhibition of Cdk2-cyclinA kinase activity. However, overactivation of Cdc2-cyclinB kinase significantly occurred with 25 uM and 50 uM LOR treatment by phosphorylation of cdc25c and inactivation of Myt1, but Cdc2-cyclinB kinase activity was down regulated when treated LOR 50 uM compared with 25 uM These results suggested that down regulation of Cdc2-cyclinB kinase activity was the major reason of G2/M arrest.