Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo |
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| Authors: | Yung‐Ting Hsiao Chao‐Lin Kuo Jen‐Jyh Lin Wen‐Wen Huang Shu‐Fen Peng Fu‐Shin Chueh Da‐Tian Bau Jing‐Gung Chung |
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| Affiliation: | 1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;2. Department of Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan;3. Division of Cardiology, China Medical University Hospital, Taichung, Taiwan;4. Department of Respiratory Therapy, China Medical University, Taichung, Taiwan;5. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan;6. Department of Food Nutrition and Health Biotechnology, Asia University, Wufeng, Taichung, Taiwan;7. Graduate Institute of Biomedical and Sciences, China Medical University, Taichung, Taiwan;8. Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, TaiwanDa‐Tian Bau and Jing‐Gung Chung contributed equally to this work.;9. Department of Biotechnology, Asia University, Taichung, TaiwanDa‐Tian Bau and Jing‐Gung Chung contributed equally to this work. |
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| Abstract: | Gefitinib has been used for cancer patients and curcumin (CUR), demethoxycurcumin (DMC), or bisdemethoxycurcumin (BDMC) also shown to induce cancer cell apoptosis. However, no report shows the combination of gefitinib with, CUR, DMC, or BDMC induce cell apoptosis and autophagy in human oral cancer cells. In this study, we investigated the effects of gefitinib with or without CUR, DMC, or BDMC co‐treatment on the cell viability, apoptotic cell death, autophagy, mitochondria membrane potential (MMP), and caspase‐3 activities by flow cytometry assay and autophagy by acridine orange (AO) staining in human oral cancer SAS cells. Results indicated that gefitinib co‐treated with CUR, DMC, or BDMC decreased total viable cell number through the induction of cell apoptosis and autophagy and decreased the levels of MMP and increased caspase‐3 activities in SAS cells. Western blotting indicated that gefitinib combined with CUR, DMC, or BDMC led to decrease Bcl‐2 protein expression which is an antiapoptotic protein and to increase ATG5, Beclin 1, p62/SQSTM1, and LC3 expression that associated with cell autophagy in SAS cells. Gefitinib combined with CUR and DMC led to significantly reduce the tumor weights and volumes in SAS cell xenograft nude mice but did not affect the total body weights. Based on those observations, we suggest that the combination of gefitinib with CUR, DMC, and BDMC can be a potential anticancer agent for human oral cancer in future. |
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| Keywords: | gefitinib curcumin demethoxycurcumin bisdemethoxycurcumin apoptosis autophagy SAS cells |
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