Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Sensitization of the Apoptotic Effect of ${\gamma}$-Irradiation in Genistein-pretreated CaSki Cervical Cancer Cells

  • Shin, Jang-In (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Shim, Jung-Hyun (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Ki-Hong (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Choi, Hee-Sook (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Jae-Wha (Cellomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hee-Gu (Cellomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Bo-Yeon (Cellomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Sue-Nie (Division of Genetic Toxicology, National Institute of Toxicological Research, Korea food & Drug Administration) ;
  • Park, Ok-Jin (Department of Nutrition, Hannam University) ;
  • Yoon, Do-Young (Department of Bioscience and Biotechnology, Konkuk University)
  • Published : 2008.03.31
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Abstract

Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only ${\gamma}$-irradiation led to cell cycle arrest at the $G_1$ phase. On the other hand, co-treatment with genistein and ${\gamma}$-irradiation caused a decrease in the $G_1$ phase and a concomitant increase up to 56% in the number of $G_2$ phase. In addition, co-treatment increased the expression of p53 and p21, and Cdc2-tyr-15-p, supporting the occurrence of $G_2/M$ arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, down regulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and ${\gamma}$-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and ${\gamma}$-irradiation almost completely prevented irradiation-induced COX-2 expression and $PGE_2$ production. Co-treatment with genistein and ${\gamma}$-irradiation inhibited proliferation through $G_2/M$ arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.

Keywords

References

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