| Y.J. Wang, J.H.Jeng, R.J. Chen, H. Tseng, L.C.Chen, Y.C. Liang, C.H. Lin, C.H. Chen, J.S. Chu, W.L. Ho, Y.S. Ho |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=34 ------>confirm_bywho=sheujr ------>insert_bywho=tsenghow ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=210 ------>medlineContent= ------>unit=E0200 ------>insert_date=20021005 ------>iam=4 ------>update_date= ------>author=?? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Molecular Carcinogennesis ------>paper_name=Ketoconazole Potentiates the Antitumor Effects of Nocodazole: In Vivo Therapy for Human Tumor Xenografts in Nude Mice ------>confirm_date=20031016 ------>tch_id=085005 ------>pmid=12203371 ------>page1=199 ------>fullAbstract=Our previous studies demonstrated that the oral antifungal agent ketoconazole (KT) induces apoptosis and G0/G1 phase cell cycle arrest in human cancer cell lines. In this study, we first demonstrated that KT (1 microM) potentiated the apoptotic effects of nocodazole (ND, 1 nM) in COLO 205 cancer cells. We further demonstrated the therapeutic efficacy of a combined treatment of KT (50 mg/kg/three times per week) and ND (5 mg/kg/three times per week) in vivo by treating athymic mice bearing COLO 205 tumor xenografts. The antitumor effects of ND were significantly potentiated by KT in mice after 6 wk of treatment. No gross signs of toxicity were observed in mice receiving these treatment regimens. The apoptotic cells were detected in a microscopic view of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and by observation of DNA fragmentation in KT + ND-treated tumor tissues. The levels of cell cycle regulatory proteins were determined by Western blot analysis. Treatment with KT inhibits tumor growth through elevation of p53, p21/CIP1, and p27/KIP1 as well as inhibition of cyclin D3 and cyclin-dependent kinase 4 protein expression. Immunohistochemical staining analysis showed that p53, p21/CIP1, and p27/KIP1 immunoreactivity were induced in the tumor tissues. To clarify the roles of the p21/CIP1 and p27/KIP1 protein expression involved in G(0)/G(1) arrest and/or apoptosis induced by a combined treatment with KT and ND, antisense oligodeoxynucleotides (ODNs) specific to p21/CIP1 and p27/KIP1 were used. Our results demonstrated that apoptotic phenomena, including BAX induction and cytochrome C released from mitochondria induced by KT + ND, were significantly attenuated by pretreatment the cells with the p27/KIP1-specific antisense ODNs. These results indicate that p27/KIP1 protein does indeed play a critical role in the KT + ND-induced apoptosis. Our study revealed the molecular mechanism of KT + ND in regression of the tumor growth. The apoptotic effects of KT in a great variety of cancer cells make it a very attractive agent for cancer chemotherapy. ------>tmu_sno=None ------>sno=6026 ------>authors2=None ------>authors3=None ------>authors4=None ------>authors5=None ------>authors6=None ------>authors6_c=None ------>authors=Y.J. Wang, J.H.Jeng, R.J. Chen, H. Tseng, L.C.Chen, Y.C. Liang, C.H. Lin, C.H. Chen, J.S. Chu, W.L. Ho, Y.S. Ho ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Ketoconazole potentiates the antitumor effects of nocodazole: In vivo therapy for human tumor xenografts in nude mice. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho= ------>publish_year=2002 ------>submit_flag= ------>publish_month=None |