Effects of a novel tripeptide, tyroserleutide (YSL), on cell cycle progression of human hepatocellular carcinoma.
The objective of this study was to develop a new small molecular peptide, tyrosyl-seryl-leucine (tyroserleutide, YSL), as an anticancer drug. Our study investigated the effects of YSL on human hepatocellular carcinoma and cyclin, and explored its antitumor mechanism in vitro. In-vitro effects of YSL on human hepatocarcinoma cell BEL-7402 were assayed by the MTS (dimethylthiazol-carboxymethoxyphenyl-sulfophenyl - tetrazolium inner salt) method. The ultrastructure of tumor cells was observed by electron microscopy. DNA ladder was used to investigate apoptosis of BEL-7402 cells. The effects of YSL on the cell cycle of BEL-7402 cells were determined by flow cytometry. Expression of PCNA, P21, and P27 were investigated by real-time PCR and western blot in BEL-7402 cells. YSL inhibited the proliferation of BEL-7402 cells in vitro, induced DNA fragmentation, and changed their ultrastructure evidently, resulting in the necrosis and apoptosis of tumor cells. YSL interrupted cell cycle of tumor cells at G0/G1 and postponed their proceedings. YSL markedly enhanced the mRNA and protein expression of P21 and P27, and decreased the expression of PCNA of tumor cells. In conclusion, YSL significantly inhibited the growth of human hepatocellular carcinoma BEL-7402 cells and its anti-tumor effects may result from the upregulation of cyclin P21 and P27, and downregulation of cyclin PCNA.
Wang
Chong
C
Department of Immunology, Tianjin Medical University, Tianjin, 300070, China.
Wang
Song
S
Lu
Rong
R
Zhao
Lan
L
Zhu
Zhi-Feng
ZF
Xu
Qiong
Q
Lv
Jun-Qiang
JQ
Wang
Lan-Lan
LL
Fu
Zheng
Z
Lin
Gang
G
Yao
Zhi
Z
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000187:drug effects / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009842:Oligopeptides; D018809:Proliferating Cell Nuclear Antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27; C484773:H-Tyr-Ser-Leu-OH