title: Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways.
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.
authors.affiliation: School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tai-Long
authors.initials: TL
authors.lastname: Pan
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Yu-Chiang
authors.initials: YC
authors.lastname: Hung
authors.forename: Chun-Hsun
authors.initials: CH
authors.lastname: Huang
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Rau
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D017239:Paclitaxel / Q000494:pharmacology; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D020543:Proteome; C021751:tanshinone; D017239:Paclitaxel
keywords: Apoptosis; Cell biology; Cervix cancer; Reticulum stress; Tanshinone IIA