Antiproliferative action of valorphin in cell cultures.
The antiproliferative effects of the haemoglobin beta-chain fragment (33-39) (valorphin or VV-haemorphin-5) were studied in a panel of tumour cell lines and normal cells of different origin, using various methods of activity determination (trypan blue inclusion test, sulphorhodamine B staining, MTT staining, flow cytometry and clonogenic test). Valorphin suppressed the proliferation of tumour cells by 25%-95%, depending on the cell line. The maximal valorphin activity was detected in transformed cells of fibroblastic (L929) and epithelial (MCF-7) origin, transformed haematopoietic cells (K562, HL-60) being less sensitive. In normal cells, valorphin activity was several fold lower (10%-15%). A study of the dynamics of cell proliferation in L929 cells using a visual cell count and flow cytometry showed that valorphin induced reversible and relatively short (24 h) S-phase arrest of cell proliferation, accompanied by a reversible increase of cell size. The proliferation delay was followed by a comparatively long period of reversible resistance of the cells to the peptide (96 h) when the cells are dividing at normal rate. The same dynamics were demonstrated for A549, MCF-7 and primary murine breast carcinoma cells. On the basis of the data obtained, a pattern of regulation of cell growth by valorphin is suggested.
Blishchenko
Elena
E
Institute of Bioorganic Chemistry, Moscow, Russia.
Sazonova
Olga
O
Surovoy
Andrei
A
Khaidukov
Sergei
S
Sheikine
Yury
Y
Sokolov
Dmitry
D
Freidlin
Irina
I
Philippova
Marina
M
Vass
Arpad
A
Karelin
Andrei
A
Ivanov
Vadim
V
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D019008:Drug Resistance, Neoplasm; D005260:Female; D018922:HL-60 Cells; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D006454:Hemoglobins; D010446:Peptide Fragments