Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy

Agostino Molteni, Sue Heffelfinger, John E. Moulder, Bruce Uhal, William Castellani

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

There is significant evidence that both angiotensin I converting enzyme inhibitors (ACEI) and type 1 and type 2 angiotensin 2 (A2) receptor blockers may inhibit tumor growth. The finding is supported by many reports where these two classes of drugs showed cytostatic effects on the cultures of several lines of both normal and neoplastic cells. These drugs often transformed the cellular biochemical structures, especially in neoplastic cell lines. The same drugs also delayed the growth of different types of tumors in a variety of experimental animals (breast and lung carcinoma in mice; sarcomas, squamous cell carcinomas and hepatocellular carcinomas in rats), and there are a few reports of successful treatment of a limited number of cases of Kaposi sarcoma and gliomas with these drugs. Retrospective studies in hypertensive subjects treated with ACEI or A2 receptor blockers also seem to indicate that the incidence and growth of different neoplasms was delayed when these patients were compared to hypertensive patients receiving alternate medications. There is strong indication that the pharmacologic effect of these drugs may be exerted by reduction or inhibition of the synthesis of angiotensin 2. A2 is a powerful mitogen and its effect on cellular growth is exerted through stimulation of many factors, including transforming growth factor β (TGFβ), epidermal growth factor (EGF), smooth muscle actin (SMA), and tyrosine kinase. A2 also regulates apoptotic mechanisms and angiogenesis. The pharmacologic action of most of these drugs, however, is not necessarily limited to downregulaton of A2. Many ACEI, especially those containing the sulfhydryl (SH group), possess antioxidant or metalloprotease inhibitory properties per se. These experimental and retrospective data justify clinical testing of these drugs in appropriate randomized trials. Several such trials are currently in process. If these trials confirm the experimental and retrospective studies, these agents will provide a significant contribution to the therapeutic treatment of many malignancies in humans.

Original languageEnglish (US)
Pages (from-to)451-460
Number of pages10
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume6
Issue number5
DOIs
StatePublished - Jan 1 2006

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Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Angiotensins
Drug Therapy
Pharmaceutical Preparations
Neoplasms
Growth
Angiotensin II Type 2 Receptor Blockers
Retrospective Studies
Pharmacologic Actions
Kaposi's Sarcoma
Angiotensin Receptor Antagonists
Cytostatic Agents
Transforming Growth Factors
Metalloproteases
Cellular Structures
Mitogens
Epidermal Growth Factor
Glioma
Sarcoma

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

Cite this

Molteni, Agostino ; Heffelfinger, Sue ; Moulder, John E. ; Uhal, Bruce ; Castellani, William. / Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy. In: Anti-Cancer Agents in Medicinal Chemistry. 2006 ; Vol. 6, No. 5. pp. 451-460.
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Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy. / Molteni, Agostino; Heffelfinger, Sue; Moulder, John E.; Uhal, Bruce; Castellani, William.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 6, No. 5, 01.01.2006, p. 451-460.

Research output: Contribution to journalReview article

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