Effect of serum depletion on centrosome overduplication and death of human pancreatic cancer cells after exposure to radiation

• Published in: Cancer letters 2001-09, Vol.170 (1), p.81-89
• Main Authors: Shono, Masaki, Sato, Norihiro, Mizumoto, Kazuhiro, Minamishima, Yohji A., Nakamura, Masafumi, Maehara, Naoki, Urashima, Taro, Saimura, Michiyo, Qian, Liwu, Nishio, Shoko, Nagai, Eishi, Tanaka, Masao
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Death - radiation effects; Centrosome; Centrosome - radiation effects; Culture Media, Serum-Free; Humans; Medical sciences; Mitosis - radiation effects; Mitotic cell death; Multinucleated cell; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Radiation; Radiation therapy and radiosensitizing agent; Serum depletion; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00533-X

The tumor microenvironment is one of the key factors affecting the cellular response to radiation; however, the influence of serum concentration on tumor radiosensitivity remains poorly understood. We recently discovered that γ-irradiation of tumor cells causes centrosome overduplication, which may lead to lethal nuclear fragmentation through the establishment of multipolar mitotic spindles. In the present study, we investigated the effect of serum depletion on radiation-induced cell death in relation to the centrosome dynamics in human pancreatic cancer cells. Exposure of Capan-1 cells to γ-irradiation resulted in a time-dependent increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death. Treatment of irradiated cells with serum depletion drastically accelerated centrosome overduplication and the formation of multipolar spindles, resulting in increased nuclear fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed that the reduced serum level increased the population of cells arrested in the G2/M phase, which might be responsible for the abnormal centrosome accumulation. These findings suggest that serum concentration can influence radiation-induced cell killing through modulating cell cycle progression and possibly centrosome overduplication.