Effects of tetrazanbigen on the protein expression in human hepatocellular carcinoma cell line QGY-7701.
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.
Yuan
Yonghua
Y
Department of Medicinal Chemistry, Research Laboratory of Pharmaceutical Chemistry and Biomaterials, Chongqing Engineering Research Center of Drugs, School of Pharmacy, Chongqing, China. yonghuayuancq@163.com
Li
Wei
W
Li
Longjiang
L
Yang
Xiaolan
X
Gu
Rong
R
Liu
Huabo
H
Huang
Kaishun
K
Yu
Yu
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D006067:Gonanes / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D011506:Proteins / Q000378:metabolism*; D020543:Proteome
D000970:Antineoplastic Agents; D001391:Azo Compounds; D006067:Gonanes; D011506:Proteins; D020543:Proteome; C552897:tetrazanbigen