Modulation of tumor cell proliferation and apoptosis by polyamine depletion in cells of head and neck squamous cell carcinomas

These studies were carried out to examine the capacity of cu-difluoromethyl ornithine (DFMO) to modulate cell proliferation and apoptosis in cells of s quamous cell carcinomas (SCCs) of the head and neck. Exposure of cells to D EMO (5 mM for 48 h) depleted intracellular putrescine and spermidine levels (greater than 5-fold) and inhibited proliferation of the cells without man ifestation of cytotoxicity as measured by a clonogenic assay, Exposure of t he cells to DEMO did not influence the survival response after exposure to single-dose radiation between 0 and 10 Gy, Treatment of polyamine-depleted cells with 200 nM staurosporine amplified apoptosis 65% (1.65-fold) over th at in controls, as determined by flow cytometry, The increased apoptosis af ter DEMO treatment was effectively inhibited by the addition of 1 mM putres cine or spermidine. Cleavage of poly(ADP-ribose) polymerase (PARP) illustra ted that the staurosporine treatment induced apoptosis in the cells within 6 h, Analysis of PARP cleavage indicated that treatment with DEMO accelerat ed the kinetics of progression of apoptosis but did not influence the sensi tivity of cells to 10 nM-1 mu M staurosporine. These data suggest an involv ement of endogenous polyamines in modulation of proliferation kinetics and apoptosis in human SCCs and suggest opportunities to explore new therapeuti c strategies in head and neck cancer patients to be treated with radiation therapy. (C) 1999 by Radiation Research Society.