Effects of tetrazanbigen on the protein expression in human hepatocellular carcinoma cell line QGY-7701 |
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Authors: | Yonghua Yuan Wei Li Longjiang Li Xiaolan Yang Rong Gu Huabo Liu Kaishun Huang Yu Yu |
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Institution: | 1. Department of Medicinal Chemistry,Research Laboratory of Pharmaceutical Chemistry and Biomaterials, Chongqing Engineering Research Center of Drugs, School of Pharmacy;Pharmacy of Children's Hospital, Chongqing Medical University, Chongqing 400016,China 2. Department of Medicinal Chemistry,Research Laboratory of Pharmaceutical Chemistry and Biomaterials, Chongqing Engineering Research Center of Drugs, School of Pharmacy 3. Pharmacy of Children's Hospital, Chongqing Medical University, Chongqing 400016,China |
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Abstract: | Summary Tetrazanbigen (TNBG) is a novel synthetic antitumor drug with significant antitumor effects on common solid tumors in vitro and in vivo. It may lead to death of cancer cells through a tumor-associated lipoidosis mechanism, and result in lipid droplets (LDs)
accumulation at the cytoplasm. In this study, the effects of TNBG on protein expression in human hepatocellular carcinoma
cell line QGY-7701 were studied for elucidating its antitumor mechanism. The proteins extracted from TNBG-treated human hepatocellular
carcinoma cell line QGY-7701 were analyzed and compared with control cells by two-dimensional gel electrophoresis. The differential
proteins were identified by matrix-associated laser desorption ionization time-of-flight mass (MALDI-TOF-MS) spectrometry.
Two proteins of interest, the levels of which were significantly increased in TNBG-treated cells, were further characterized
by Western blot analysis. The results showed a total of 846±23 spots in control cells and 853±30 spots in TNBG-treated cells.
Twenty-six up-regulated or down-regulated proteins were found by analyzing differential proteomic 2-DE map. Eleven of them
were identified by mass spectrometry. They were protein disulfide-isomerase precursor, 94 kD glucose-regulated protein, heat
shock protein (HSP) 90-alpha, ATP-citrate lyase, HMG-CoA reductase, glucose-6-phosphate 1-dehydrogenase, very-long-chain specific
acyl-CoA dehydrogenase, squalene synthetase, sterol regulatory element-binding protein 1, fructose-bisphosphate aldolase A,
and peroxiredoxin-1. These up-regulated or down-regulated proteins are mostly related to lipid metabolism. The TNBG antitumor
mechanism is probably to influence tumor lipid metabolism, resulting in accumulation of LDs in tumor cells.
This project was supported by grants from National Natural Sciences Foundation of China (No. 30772595, No. 3037163 2 and No.
30171070), National Foundation for New Drug Research and Development of China (No. 96-501-5-6), and Chongqing Municipal Sciences
Technology Commission (Yu Ke Fa 20021425). |
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Keywords: | tetrazanbigen antitumor lipid metabolism proteomics |
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