Angiotensin-converting enzyme inhibitor, Enalapril, inhibits tumor growth and potentiates the antitumor efficacy of 5-FU in colorectal cancer

Abstract

OBJECTIVE: Colorectal cancer (CRC) is among the leading causes of cancer-related death, indicating the need for the identification of novel therapeutic approaches to increase the activity of current therapy or have better efficacy. Angiotensin-converting enzyme (ACE) is being reported to be associated with aggressive behaviors of CRC cells and poor prognosis. Here we explored the therapeutic potency of targeting ACE by Enalapril in CRC in vivo model. MATERIALS AND METHODS: A xenograft model of CRC was used to investigate the effects of Enalapril alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin and Eosin and Masson trichrome staining) and biochemical studies of Malondialdehyde (MDA), total thiols, superoxide dismutase (SOD) and catalase (CAT) activities. RESULTS: Enalapril reduced tumor growth and increased tumor necrosis; this effect was more pronounced in Enalapril plus 5-FU combination. Enalapril/5-FU was able to decrease tumor fibrosis and collagen content. ACE inhibitors also increased MDA level, as an oxidative stress marker, while reducing total thiol group levels, SOD and CAT enzyme activity. CONCLUSIONS: Our findings provide a novel insight on the therapeutic potential targeting of the renin–angiotensin system as a new therapeutic option in combination with current therapeutic agents 5-FU in the treatment of CRC.

Keywords

• colorectal cancer
• enalapril
• angiotensin-converting enzyme