Sensitization of the apoptotic effect of γ-irradiation in genistein-pretreated CaSki cervical cancer cells

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Title
Sensitization of the apoptotic effect of γ-irradiation in genistein-pretreated CaSki cervical cancer cells
Author(s)
J I Shin; J H Shim; K H Kim; H S Choi; Jae Wha KimHee Gu LeeBo Yeon Kim; S N Park; O J Park; D Y Yoon
Bibliographic Citation
Journal of Microbiology and Biotechnology, vol. 18, no. 3, pp. 523-531
Publication Year
2008
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 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, co-treatment 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 cotreatment-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. Gamma-irradiation 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.
Keyword
γ-irradiationapoptosisCaSki cervical cancer cellsgenisteinROS
ISSN
1017-7825
Publisher
Korea Soc-Assoc-Inst
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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