https://scholars.lib.ntu.edu.tw/handle/123456789/634496
標題: | Anticancer Activity and Molecular Mechanisms of an Ursodeoxycholic Acid Methyl Ester-Dihydroartemisinin Hybrid via a Triazole Linkage in Hepatocellular Carcinoma Cells | 作者: | Hsu, Ya-Fen FAN-LU KUNG Huang, Tzu-En Deng, Yi-Ning JIH-HWA GUH Marchetti, Paolo Marchesi, Elena Perrone, Daniela Navacchia, Maria Luisa LIH-CHING HSU |
關鍵字: | anticancer; apoptosis; autophagy; bile acid–dihydroartemisinin hybrids; hepatocellular carcinoma; oxidative stress | 公開日期: | 3-三月-2023 | 卷: | 28 | 期: | 5 | 起(迄)頁: | 2358 | 來源出版物: | Molecules (Basel, Switzerland) | 摘要: | Hepatocellular carcinoma is the third most common cause of cancer-related death according to the International Agency for Research on Cancer. Dihydroartemisinin (DHA), an antimalarial drug, has been reported to exhibit anticancer activity but with a short half-life. We synthesized a series of bile acid-dihydroartemisinin hybrids to improve its stability and anticancer activity and demonstrated that an ursodeoxycholic-DHA (UDC-DHA) hybrid was 10-fold more potent than DHA against HepG2 hepatocellular carcinoma cells. The objectives of this study were to evaluate the anticancer activity and investigate the molecular mechanisms of UDCMe-Z-DHA, a hybrid of ursodeoxycholic acid methyl ester and DHA via a triazole linkage. We found that UDCMe-Z-DHA was even more potent than UDC-DHA in HepG2 cells with IC50 of 1 μM. Time course experiments and stability in medium determined by cell viability assay as well as HPLC-MS/MS analysis revealed that UDCMe-Z-DHA was more stable than DHA, which in part accounted for the increased anticancer activity. Mechanistic studies revealed that UDCMe-Z-DHA caused G0/G1 arrest and induced reactive oxygen species (ROS), mitochondrial membrane potential loss and autophagy, which may in turn lead to apoptosis. Compared to DHA, UDCMe-Z-DHA displayed much lower cytotoxicity toward normal cells. Thus, UDCMe-Z-DHA may be a potential drug candidate for hepatocellular carcinoma. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/634496 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules28052358 |
顯示於: | 藥學系 |
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