Modulation of Tumor Cell Proliferation and Apoptosis by Polyamine Depletion in Cells of Head and Neck Squamous Cell Carcinomas

• Published in: Radiation research 1999-12, Vol.152 (6), p.604-610
• Main Authors: Bock, Jonathan M., Pickart, Michael A., Pink, John J., Harari, Paul M.
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Carcinoma, Squamous Cell - pathology; Cell cycle; Cell Division - drug effects; Cell Division - radiation effects; Cell growth; Cell lines; Cell Survival - drug effects; Cell Survival - radiation effects; Cytometry; Dose-Response Relationship, Drug; Eflornithine - pharmacology; Head; Head and neck neoplasms; Head and Neck Neoplasms - pathology; Humans; Kinetics; Medical sciences; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Poly(ADP-ribose) Polymerases - metabolism; Polyamines; Polyamines - metabolism; Radiation therapy and radiosensitizing agent; Space life sciences; Squamous cell carcinoma; Staurosporine - pharmacology; Time Factors; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured; Tumor Stem Cell Assay; Tumors
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3580255

These studies were carried out to examine the capacity of α-difluoromethylornithine (DFMO) to modulate cell proliferation and apoptosis in cells of squamous cell carcinomas (SCCs) of the head and neck. Exposure of cells to DFMO (5 mM for 48 h) depleted intracellular putrescine and spermidine levels (greater than 5-fold) and inhibited proliferation of the cells without manifestation of cytotoxicity as measured by a clonogenic assay. Exposure of the cells to DFMO 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 that in controls, as determined by flow cytometry. The increased apoptosis after DFMO treatment was effectively inhibited by the addition of 1 mM putrescine or spermidine. Cleavage of poly(ADP-ribose) polymerase (PARP) illustrated that the staurosporine treatment induced apoptosis in the cells within 6 h. Analysis of PARP cleavage indicated that treatment with DFMO accelerated the kinetics of progression of apoptosis but did not influence the sensitivity of cells to 10 nM-1 μM staurosporine. These data suggest an involvement of endogenous polyamines in modulation of proliferation kinetics and apoptosis in human SCCs and suggest opportunities to explore new therapeutic strategies in head and neck cancer patients to be treated with radiation therapy.