Visual characterization of targeted effect of holo-transferrin-tagged dihydroartemisinin on human breast cancer cells

作     者：XIE WeiLing YANG PeiHui ZENG Xin WANG Hui CAI HuaiHong CAI JiYe 

作者机构：Department of Chemistry Jinan University Guangzhou 510632 China Key Laboratory of Optoelectronic Information and Sensing Technologies of Guangdong Higher Education Institutes Jinan University Guangzhou 510632 China 

出 版 物：《Chinese Science Bulletin》 (科学通报(英文版))

年 卷 期：2010年第55卷第22期

页      面：2390-2395页

核心收录：

学科分类：0710[理学-生物学] 1008[医学-中药学(可授医学、理学学位)] 07[理学] 071007[理学-遗传学] 10[医学] 

基　　金：supported by the National Key Basic Research and Devel-opment Program of China (2010CB833603) the National Natural Science Foundation of China (30828023) 

主　　题：人乳腺癌细胞 双氢青蒿素 视觉特性 全息 转铁蛋白受体 原子力显微镜 转移因子 细胞毒作用 

摘      要：Targeted drugs could significantly reduce cytotoxic effect and increase therapeutic activity. Dihydroartemisinin (DHA) has been shown to be effective in killing cancer cells. However, it exhibits non-targeted property. Holo-transferrin (TF) is a suitable drug-carrier to target cancer cells, because cancer cells need iron uptake by the TF-mediated mechanism to maintain their uncontrolled growth. Furthermore, TF receptors (TF-R) are highly expressed on cancer cell surfaces. In this paper, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the different killing effect of 4-(12-Dihydroartemisininoxy) Benzoic Acid Hydrozide-transferrin (DBAH-TF) on human breast cancer cells (MCF-7) cells and human normal breast (HNB) cells, and atomic force microscopy (AFM) was used to visually observe the targeted effect of DBAH-TF on MCF-7 cells. MTT results show that DBAH-TF is 172 times more potent than DHA in killing MCF-7 cells, while the cytotoxic effect of DBAH-TF on HNB cells is merely 1/33 to DHA. Also, the killing effect of DBAH-TF on MCF-7 cells is 286 times that on HNB cells, showing targeted effect. Moreover, there are distinct differences in ultrastructures of cellular surfaces after DBAH-TF and DHA treatment. Through AFM imaging, many characteristic holes were observed on the cancer cell surface after being effected by DBAH-TF, which differ from the holes with irregular shapes affected by DHA. These results visually show that the DBAH-TF targeted drug has more potent killing effect on MCF-7 cells compared with DHA.