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 MIT 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 (1,929) and epithelial (MCF 7) origin transformed haematopoietic cells (K5b2 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 irreversible 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 Copyright (C) 2002 European Peptide Society and John Wiley Sons Ltd.