Prevention of mouse lung tumors by targretin.

Targretin has indicated chemotherapeutic activity against nonsmall-cell lung cancer and chemoprevention in rat mammary gland. Therefore, targretin was evaluated for the prevention of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) and vinyl carbamate-induced lung tumors in female strain A mice. Three experiments were performed: (i) a dose-response study with vinyl carbamate-induced tumors; (ii) a limited treatment study also with vinyl carbamate and (iii) prevention of NNK-induced tumors. In the dose-response study, 0, 10, 30, 100 and 300 mg/kg targretin were administered after vinyl carbamate. Dose levels of 30 mg/kg and greater significantly decreased tumor multiplicity by >19%. However, the efficacy of 30 and 300 mg/kg was not significantly different demonstrating a shallow dose-response relationship. In the limited treatment study, 200 mg/kg targretin was administered to the mice from 4-13, 4-19, 4-25 and 23-25 weeks after vinyl carbamate. Administering targretin from weeks 4-19 and 4-25 decreased the multiplicity of tumors from 35.3 +/- 1.43 to 29.1 +/- 1.51 and 25.0 +/- 0.93, respectively, and along with administering it from weeks 23-25 decreased tumor size. In the third study, when targretin (100 and 300 mg/kg) was administered for 3 weeks after NNK followed by a 20 weeks holding period, tumor multiplicity was reduced from 10.6 +/- 1.13 to 6.38 +/- 0.75 and 4.60 +/- 0.70, respectively. Hence, targretin demonstrated both preventive and therapeutic activity with respect to mouse lung tumors supporting its further development as a preventive and therapeutic agent for lung cancer.
AuthorsMichael A Pereira, Paula M Kramer, Ronald Nines, Yue Liu, Fadel S Alyaqoub, William T Gunning, Vernon E Steele, Ronald A Lubet
JournalInternational journal of cancer. Journal international du cancer (Int J Cancer) Vol. 118 Issue 9 Pg. 2359-62 (May 1 2006) ISSN: 0020-7136 [Print] United States
PMID16331605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright2005 Wiley-Liss, Inc.
Chemical References
  • Anticarcinogenic Agents
  • Nitrosamines
  • Tetrahydronaphthalenes
  • Urethane
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • vinyl carbamate
  • bexarotene
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Chemoprevention
  • Dose-Response Relationship, Drug
  • Female
  • Lung Neoplasms (prevention & control)
  • Mice
  • Neoplasms, Experimental (prevention & control)
  • Nitrosamines (administration & dosage)
  • Tetrahydronaphthalenes (pharmacology)
  • Urethane (administration & dosage, analogs & derivatives)

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