Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C-phycocyanin.
The aim of this study was to investigate the pro-apoptotic mechanism of C-phycocyanin (C-PC)-mediated photodynamic therapy (PDT) in a murine tumor model and cultured MCF-7 cells. The mice were divided into four groups: control, He-Ne laser radiation, C-PC treatment, and C-PC treatment + He-Ne laser radiation. The effects of C-PC and/or laser on immune organs, immunocyte proliferation, tumor genesis, and apoptosis-related proteins expressions were investigated by immunohistochemistry, in situ hybridization, MTT, electron microscope, western blot, and immunofluorescence assay. The results showed that He-Ne laser treatment alone showed marginal effects. In C-PC-treated mice, the weight of immune organs, proliferation of immunocytes, and expression of pro-apoptotic Fas protein were increased, whereas the tumor weight and the expressions of anti-apoptotic proteins (NF-kappaB and P53) and CD44 mRNA were comparatively decreased. In vitro, C-PC was able to inhibit MCF-7 cell proliferation and cause ultrastructural changes including microvilli loss, formation of membrane blebs, and chromatin condensation. Moreover, C-PC treatment could activate caspase-9 expression, induce cytochrome c release, and downregulate Bcl-2 expression. When combined with He-Ne laser irradiation, the effects of C-PC treatment were further enhanced. Facilitating the apoptosis signals transduction and finally leading to the apoptosis of MCF-7 cells may be the mechanism of the anti-tumor activities of C-PC-mediated PDT.
Li
Bing
B
Department of Biology, Medical College of Qingdao University, Qingdao, China. libing_516@yahoo.com.cn
Chu
Xianming
X
Gao
Meihua
M
Li
Wuxiu
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010778:Photochemotherapy; D010798:Phycocyanin / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology*
D003574:Cytochrome c Group; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D010798:Phycocyanin; C076615:cytochrome c''; D045304:Cytochromes c; D053453:Caspase 9