Coumarin derivative 7-isopentenyloxycoumarin induces in vivo antitumor activity by inhibit angiogenesis via CCL2...

Area of Science:

• Pharmacology
• Oncology
• Natural Products Chemistry

Background:

• Cancer remains a leading global cause of death, necessitating novel therapeutic strategies.
• Natural products serve as valuable scaffolds for developing new anticancer agents with improved efficacy and reduced toxicity.
• 7-isopentenyloxycoumarin (UMB-07) is a coumarin derivative exhibiting promising antitumor activity.

Purpose of the Study:

• To evaluate the in vivo toxicity of UMB-07.
• To elucidate the mechanism underlying the antitumor action of UMB-07.
• To assess the potential of UMB-07 as a less toxic anticancer therapeutic.

Main Methods:

• In vitro hemolysis and in vivo micronucleus and acute toxicity assays were performed.
• Antitumor activity was assessed using an Ehrlich ascites carcinoma model in mice.
• Tumor volume, viable cancer cells, microvessel density, CCL2 levels, and toxicity parameters were analyzed.

Main Results:

• UMB-07 demonstrated low toxicity, with an LD50 around 1000 mg/kg and no significant hemolysis or genotoxicity.
• UMB-07 treatment (25 and 50 mg/kg) significantly reduced tumor volume and viable cancer cells.
• The compound inhibited angiogenesis by decreasing peritumoral microvessel density and CCL2 chemokine levels, without affecting cell cycle progression.

Conclusions:

• UMB-07 exhibits a favorable safety profile with minimal toxicity.
• UMB-07 effectively suppresses tumor growth through anti-angiogenic mechanisms.
• Inhibition of angiogenesis via CCL2 chemokine reduction represents a key mechanism of UMB-07's antitumor effect.