Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways |
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| Authors: | Tai‐Long Pan Pei‐Wen Wang Yu‐Chiang Hung Chun‐Hsun Huang Kun‐Ming Rau |
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| Institution: | 1. School of Traditional Chinese Medicine, Chang Gung University, , Taoyuan, Taiwan;2. Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, , Taoyuan, Taiwan;3. Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan;4. Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, , Taoyuan, Taiwan;5. Division of Hema‐Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, , Kaohsiung, Taiwan |
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| Abstract: | Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP‐homologous protein as well as apoptosis signal‐regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial‐related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance. |
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| Keywords: | Apoptosis Cell biology Cervix cancer Reticulum stress Tanshinone IIA |
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