title: Combination of 12-O-tetradecanoylphorbol-13-acetate with diethyldithiocarbamate markedly inhibits pancreatic cancer cell growth in 3D culture and in immunodeficient mice.
abstract: The aim of the present study was to determine the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocarbamate (DDTC) alone or in combination on human pancreatic cancer cells cultured in vitro and grown as xenograft tumors in nude mice. Pancreatic cancer cells were treated with either DDTC or TPA alone, or in combination and the number of viable cells was then determined by trypan blue ecxlusion assay and the number of apoptotic cells was determined by morphological assessment by staining the cells with propidium idiode and examining them under a fluorescence microscope. Treatment with DDTC or TPA alone inhibited the growth and promoted the apoptosis of pancreatic cancer cells in a concentration-dependent manner. These effects were more prominent following treatment with TPA in combination with DDTC than following treatment with either agent alone in PANC-1 cells in monolayer cultures and in 3 dimensional (3D) cultures. The potent effects of the combination treatment on PANC-1 cells were associated with the inhibition of nuclear factor-κB (NF-κB) activation and the decreased expression of Bcl-2 induced by DDTC, as shown by NF-κB-dependent reporter gene expression assay and western blot analysis. Furthermore, treatment of nude mice with DDTC + TPA strongly inhibited the growth of PANC-1 xenograft tumors. The results of the present study indicate that the administration of TPA and DDTC in combination may be an effective strategy for inhibiting the growth of pancreatic cancer.
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Nasopharyngeal Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Saquib
authors.initials: S
authors.lastname: Malik
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chang
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Huaqian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Van Doren
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004050:Ditiocarb / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; D004050:Ditiocarb; D013755:Tetradecanoylphorbol Acetate
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