Captopril as a potential inhibitor of lung tumor growth and metastasis

Samir Attoub, Anne Marie Gaben, Suhail Al-Salam, M. A.H. Al Sultan, Anne John, M. Gary Nicholls, Jan Mester, Georg Petroianu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

80 Citations (Scopus)

Abstract

Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease. The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts. Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P = 0.088). There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.

Original languageEnglish
Title of host publicationRecent Advances in Clinical Oncology
PublisherBlackwell Publishing Inc.
Pages65-72
Number of pages8
ISBN (Print)9781573317009
DOIs
Publication statusPublished - Sep 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1138
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Captopril
  • Lung tumor
  • Metastasis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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