- 作者: Huei-Sheng Huang; Zi-Miao Liu; Ling Ding; Wen-Chang Chang; Pei-Yin Hsu; Shu-Hui Wang; Ching-Chi Chi; Cheng-Hsin Chuang
- 作者服務機構: 1 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan;; 2 Institute of Mirco-Electro-Mechanical-System Engineering, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ; 3 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ; 4 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; ; 5 Department of Dermatology; Chang Gung Memorial Hospital, Chiayi, Taiwan; ; 6 Electronics Research & Service Organization, Industrial Technology Research Institute, Tainan, Taiwan
- 中文摘要: --
- 英文摘要: While arsenic trioxide (As2O3) is an infamous carcinogen, it is also an effective chemotherapeutic agent for acute promyelocytic leukemia and some solid tumors. In human epidermoid carcinoma A431 cells, we found that As2O3 induced cell death in time- and dose-dependent manners. Similarly, dependent regulation of the p21WAF1/CIP1 (p21) promoter, mRNA synthesis, and resultant protein expression was also observed. Additionally, transfection of a small interfering RNA of p21 could block the As2O3-induced cell growth arrest. The As2O3-induced p21 activation was attenuated by inhibitors of EGFR and MEK in a dose-dependent manner. Using a reporter assay, we demonstrated the involvement of the EGFR-Ras-Raf-ERK1/2 pathway in the promoter activation. In contrast, JNK inhibitor enhanced the As2O3-Induced p21 activation, also in a dose-dependent fashion. Over-expression of a dominant negative JNK plasmid likewise also enhanced this activation. Furthermore, MEK inhibitor attenuated the anti-tumor effect of As2O3. In contrast, in combination with JNK inhibitor and As2O3 enhanced cellular cytotoxicity. Therefore, we conclude that in A431 cells the ERK1/2 and JNK pathways might differentially contribute to As2O3-induced p21 expression and then due to cellular cytotoxicity.
- 中文關鍵字: --
- 英文關鍵字: Arsenic trioxide, ERKl/2, JNK, p21WAF1/CIP1