Journal
CHINESE SCIENCE BULLETIN
Volume 55, Issue 22, Pages 2390-2395Publisher
SCIENCE PRESS
DOI: 10.1007/s11434-010-3284-3
Keywords
dihydroartemisinin; holo-transferrin; breast cancer cells; atomic force microscopy; cytotoxicity
Categories
Funding
- National Key Basic Research and Development Program of China [2010CB833603]
- National Natural Science Foundation of China [30828023]
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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.
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