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Cimetidine inhibits angiogenesis and suppresses tumor growth

Takeshi Natori1, Masataka Sata, Ryozo Nagai

  • 1Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 3, 2005
PubMed

Insights

Cimetidine, a histamine type-2 receptor antagonist, was found to suppress colon cancer growth in mice by inhibiting tumor angiogenesis. This drug reduced tumor size and neovascularization without affecting cancer cell proliferation directly.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Histamine type-2 receptor antagonists, like cimetidine, have shown potential in improving cancer patient survival.
  • The precise mechanisms underlying cimetidine's anti-cancer effects, particularly concerning tumor growth and vascularization, require further investigation.
  • Solid tumor progression is critically dependent on the formation of new blood vessels (neovascularization).

Purpose of the Study:

  • To investigate the impact of cimetidine on tumor growth and angiogenesis in a preclinical cancer model.
  • To elucidate the specific mechanisms by which cimetidine may inhibit cancer development.

Main Methods:

  • A syngeneic mouse model of colon cancer (CMT93 cells in C57BL/6 mice) was utilized.
  • Mice were treated with either saline (control) or cimetidine, and tumor size was monitored daily.
  • Tumor angiogenesis was assessed through histological evaluation, and in vitro assays examined cancer cell proliferation and endothelial cell tube formation.

Main Results:

  • Cimetidine treatment significantly suppressed tumor growth and reduced neovascularization within the tumors.
  • Cimetidine did not affect the proliferation of colon cancer cells in vitro.
  • While vascular endothelial growth factor (VEGF) production by cancer cells remained unchanged, cimetidine impaired the ability of endothelial cells to form vascular-like tubes in vitro.

Conclusions:

  • Cimetidine exhibits anti-tumor effects, at least partially, by inhibiting tumor-associated angiogenesis.
  • The drug's mechanism involves impairing endothelial cell function rather than directly affecting cancer cell proliferation or VEGF production.
  • These findings highlight a potential therapeutic role for cimetidine in cancer treatment by targeting tumor vascularization.

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