Photodynamic therapy (PDT) of cells is a new treatment modality involving selective delivery of a photosensitive dye into target cells, followed by visible light irradiation. PDT induces cell death by excessive ROS generation. The effects of multiple photosensitizers were owing to the difference in cell types involving sensitizer-specific protein changes linked to resistance. HSP27 is regulated in response to stress and is associated with apoptotic process. The effects of HSP27 on PDT resistance are controversial and unclear. The purpose of this study was to investigate the role of HSP27 down-regulation in the PDT-induced cells and HSP27 regulation in the resistance to PDT. KB cells transfected with HSP27 siRNA were exposed to hematoporphyrin (HP) followed by irradiation at 635 nm at an energy density of 4.5 mW/cm(2). After irradiation, the effects on HSP27 down-regulation were assessed by MTT assay, flow cytometry, confocal analysis, Western blotting and caspase activity. The results of this study showed that down-regulation of HSP27 restored cell survival in HP-PDT-induced apoptotic KB cells. HSP27 down-regulation attenuated PDT-induced apoptosis through caspase-mediated pathway in KB cells. Also, HSP27 silencing regulated Bax, Bcl-2, and PARP protein expression in PDT-induced cells. Therefore, HSP27 down-regulation confers resistance to PDT through interruption of apoptotic protein activity in PDT-induced cell death. HSP27 might contribute to regulating PDT-induced apoptosis in PDT-resistant cells.

e22130 Background: Breast cancer with resistance to clinical therapy is a significant threat to live of recurrent breast cancer patients, and chemo-resistant breast cancer is increasing rapidly. During last several decades, natural stilbenoids have been studied on anticancer effects in vitro and in vivo, and resveratrol is the most famous stilbene as a leading compound in the studies of anticancer compounds derived from plants. HMPS (2-hydroxy-4-methoxyphenylstilbene) is an analogue derived from rhapontigenin (3,5,3'-trihydroxy-4'-methoxy-trans-stilbene), which is a stilbene of herbal plant Rheum undulatum. TMS (2,3',4,5'-tetramethoxystilbene), an another stilbene analogue from rhapontigenin, was reported potent anticancer effect on tamoxifen-resistant MCF-7 cells. In this study we investigated inhibitory effect of HMPS on proliferation of breast cancer and a potential for a new therapeutic candidate. Methods: We examined cell viability of MCF-7 and MDA-MB-231 by MTT assay after exposure to various concentrations of HMPS. Apoptotic cell death induced by HMPS was investigated by florescence microscopy, cell cycle analysis and western blotting. Results: Cell viability of breast cancer cells after 24 h exposure to HMPS decreased significantly, and both ER-positive and ER-negative breast cancer cells responded to HMPS. HMPS induced nucleus fragmentation and G2/M arrest followed by sub-G1 accumulation of apoptotic cells in time- and dose-dependent manner. During the process of cell death induced by HMPS, mitochondrial membrane potential was disturbed and caspase-3 and PARP cleavage were observed. Moreover, HMPS decreased cell number of LTED MCF-7 cells(Long term estradiol deprived cell) effectively. Conclusions: Our results demonstrates that proliferation inhibitory effect of HMPS is about 50-fold more potent than those of rhapontigenin and furthermore HMPS also inhibits cell growth of LTED cells which are difficult to treat therapeutic agents. Therefore, HMPS may be a potential therapeutic candidate to treat the recurrent breast cancer by alone or combination with other conventional anticancer agents. No significant financial relationships to disclose.