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KMID : 0545120080180030523
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Journal of Microbiology and Biotechnology
2008 Volume.18 No. 3 p.523 ~ p.531
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Sensitization of the Apoptotic Effect of γ-Irradiation in Genistein-pretreated CaSki Cervical Cancer Cells
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Shin Jang-In
Shim Jung-Hyun
Kim Ki-Hong
Choi Hee-Sook
Kim Jae-Wha
Lee Hee-Gu
Kim Bo-Yeon
Park Sue-Nie
Park Ock-Jin
Yoon Do-Young
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Abstract
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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 γ-irradiation led to cell cycle arrest at the G1 phase. On the other hand, co-treatment with genistein and γ-irradiation caused a decrease in the G1 phase and a concomitant increase up to 56% in the number of G2 phase. In addition, cotreatment increased the expression of p53 and p21, and Cdc2- tyr-15-p, supporting the occurrence of G2/M arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, downregulation 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 γ-irradiation in cervical cancer cells. Gammairradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and γ-irradiation almost completely prevented irradiation-induced COX-2 expression and PGE2 production. Co-treatment with genistein and γ-irradiation inhibited proliferation through G2/M arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.
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KEYWORD
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Genistein, CaSki cervical cancer cells, apoptosis, γ-irradiation, ROS
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