A cytotoxic, apoptotic, low-molecular weight factor from pineal gland

Previous studies suggest that the pineal gland may play a, role in tumour g rowth inhibition. In this respect, melatonin, as the major hormone of this gland, has been extensively studied. However, there is growing evidence for the existence of other yet unknown pineal factors that may have tumour gro wth inhibiting properties. Here we describe the partial purification of a h ighly cytotoxic low molecular weight (<400 Da) hydrophilic fraction (design ated F2M3R), starting from a porcine pineal extract (PE), via methanol prec ipitation followed by reverse-phase HPLC. F2M3R is cytotoxic for a highly a poptosis-resistant human erythroleukemia cell line (K562) at a concentratio n as low as 30 mu g/ml. The viability of the cells was not influenced by an identical prepared porcine pituitary extract or by melatonin. PE induces a poptosis in K562 cells as indicated by three different criteria: morphology , in situ TUNEL assay and bi-parametric FAGS analysis with annexin V and pr opidium iodide, but does not influence the viability of stimulated peripher al blood mononuclear cells. These observations warrant further purification and validation of the cytotoxicity in a panel of different human tumour an d non-malignant cells.