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

Masaki Shono, Norihiro Sato, Kazuhiro Mizumoto, Yohji A. Minamishima, Masafumi Nakamura, Naoki Maehara, Taro Urashima, Michiyo Saimura, Liwu Qian, Shoko Nishio, Eishi Nagai, Masao Tanaka

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalCancer Letters
Volume170
Issue number1
DOIs
Publication statusPublished - 2001 Sep 10

    Fingerprint

Keywords

  • Centrosome
  • Mitotic cell death
  • Multinucleated cell
  • Radiation
  • Serum depletion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Shono, M., Sato, N., Mizumoto, K., Minamishima, Y. A., Nakamura, M., Maehara, N., Urashima, T., Saimura, M., Qian, L., Nishio, S., Nagai, E., & Tanaka, M. (2001). Effect of serum depletion on centrosome overduplication and death of human pancreatic cancer cells after exposure to radiation. Cancer Letters, 170(1), 81-89. https://doi.org/10.1016/S0304-3835(01)00533-X