Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells.
This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 microg x kg(-1) x d(-1), 160 microg x kg(-1) x d(-1) and 320 microg x kg(-1) x d(-1) significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 microg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p < 0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.
Fu
Zheng
Z
Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
Lu
Rong
R
Li
Guoli
G
Zhao
Lan
L
Gao
Weizhen
W
Che
Xuchun
X
Jian
Xu
X
Zhou
Chunlei
C
Yao
Zhi
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000008:administration & dosage* / Q000502:physiology; D011897:Random Allocation; D020112:Rhodamine 123 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides; D020112:Rhodamine 123; C484773:H-Tyr-Ser-Leu-OH; D002118:Calcium