Faculty Collaboration Database

Modulation of tumor cell proliferation and apoptosis by polyamine depletion in cells of head and neck squamous cell carcinomas. Radiat Res 1999 Dec;152(6):604-10

Date

12/03/1999

Pubmed ID

10581530

DOI

10.2307/3580255

Scopus ID

2-s2.0-0032786902 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

These studies were carried out to examine the capacity of alpha-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 microM 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.

Author List

Bock JM, Pickart MA, Pink JJ, Harari PM

Author

Jonathan Bock MD Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apoptosis
Carcinoma, Squamous Cell
Cell Division
Cell Survival
Dose-Response Relationship, Drug
Eflornithine
Head and Neck Neoplasms
Humans
Kinetics
Poly(ADP-ribose) Polymerases
Polyamines
Staurosporine
Time Factors
Tumor Cells, Cultured
Tumor Stem Cell Assay