Abstract
Purpose: To investigate the antitumor effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on human Bel7402 hepatocarcinoma in vitro and in vivo, with preliminary exploration of its antitumor mechanism. Methods: MTT was used to observe the anticarcinogenic effects of YSL on human hepatocarcinoma Bel7402 cells in vitro. The ultrastructure of tumor cells was observed by electron microscopy. Nude mice bearing xenografts of human hepatocarcinoma Bel7402 were given daily i.p. injections of YSL or saline and an admixture of amino acids as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. The effects of YSL on the cell cycle and apoptosis of Bel7402 cells were determined by flow cytometry, and the effects on the ultrastructure of the cells by electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and proliferating-cell nuclear antigen (PCNA) immunohistochemical staining were used to investigate apoptosis in tumor tissue in nude mice. Results: In vitro YSL inhibited the proliferation of human Bel7402 tumor cells and changed their ultrastructure, resulting in the necrosis and apoptosis of the tumor cells. YSL at 80, 160, or 320 μg/kg/d inhibited tumor growth in nude mice by 40.26, 64.17, and 59.19%, respectively, which are significantly lower than the inhibition exerted by saline and an admixture of YSL amino acids (P<0.05). The ultrastructure and cell cycle of human hepatocarcinoma Bel7402 cells were changed by treatment with YSL, with a rate of apoptosis higher than that of the control group. TUNEL and PCNA analysis showed that YSL inhibited the proliferation of tumor cells and induced apoptosis at the level of the cell. Conclusions: YSL significantly inhibited human hepatocarcinoma Bel7402 growth in vitro and in vivo. The growth inhibition of the tumor may involve necrosis and apoptosis of the tumor induced by YSL.
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Abbreviations
- YSL:
-
Tyroserleutide
- MTT:
-
3-(4, 5-diemethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide
- TUNEL:
-
Terminal transferase uridyl nick end labeling
- PCNA:
-
Proliferating-cell nuclear antigen
- HCC:
-
Hepatocellular carcinoma
- FDA:
-
Food and Drug Administration
- SPF:
-
Specific-pathogen free
- DAB 3:
-
3′-diaminobenzidine tetrahydrochloride
- FBS:
-
Fetal bovine Serum
- EDTA :
-
Ethylenediaminetetraacetic acid
- ELISA:
-
Enzyme-linked immunosorbent assay
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This study was supported by grants for the National High Technology Research and Development Program of China (2004AA2Z3170) (863 Program), The National Basic Research Program(2003CCA04300)(973 Program) and a project grant (03007) from the Department of Education of China.
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Lu, R., Jia, J., Bao, L. et al. Experimental study of the inhibition of human hepatocarcinoma Bel7402 cells by the tripeptide tyroserleutide(YSL). Cancer Chemother Pharmacol 57, 248–256 (2006). https://doi.org/10.1007/s00280-005-0046-z
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DOI: https://doi.org/10.1007/s00280-005-0046-z