title: Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate Cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice.
abstract: OBJECTIVE
  To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice.
  
  
  METHODS
  Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2).
  
  
  RESULTS
  Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression.
  
  
  CONCLUSIONS
  TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.
authors.affiliation: Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08854, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Richard L
authors.initials: RL
authors.lastname: Chang
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Cui
authors.forename: Gina E
authors.initials: GE
authors.lastname: Avila
authors.forename: Vidya
authors.initials: V
authors.lastname: Hebbar
authors.forename: Mark
authors.initials: M
authors.lastname: Garzotto
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Shou-En
authors.initials: SE
authors.lastname: Lu
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.forename: Ah Ng Tony
authors.initials: AN
authors.lastname: Kong
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D017239:Paclitaxel