The Anti-angiogenic Potential of Thiosemicarbazide Derivative of Captopril (8) in Breast Cancer Cell Lines.

Angiogenesis is essential for many tumours to grow and metastasise, including breast tumours. Captopril, an Angiotensin- Converting Enzyme inhibitor is known to have anti-angiogenic activity. Recently, novel derivatives of captopril that include thiosemicarbazide moiety have shown enhanced ACE inhibition activity compared to captopril. This study aimed to assess the anti-angiogenic activity of one of these derivatives designated as (8) in the Estrogen receptor-positive MCF-7, and the Estrogen-Progesterone receptor-negative AMJ13 breast cancer cells. The study included a microarray screening for 24 angiogenic factors, and genes were confirmed by RT-qPCR. Results demonstrated a stronger anti-angiogenic effect in the MCF-7 cells compared to those on AMJ13. In MCF7, the derivative caused a significant decrease in the pro-angiogenic bFGF mRNA, VEGF-A mRNA expression, thrombopoietin protein level, PECAM -1 (CD31) mRNA, G-CSF protein, and a significant increase in the anti-angiogenic factors MIG mRNA level, IL-13 protein level, PF-4 both protein and mRNA level. The derivative also significantly decreased TIMP-1 mRNA and IFN-γ protein levels, whereas in AMJ13, a significant increase in MIG protein expression (but not mRNA), a significant decrease in IL-β protein expression, as well as thrombopoietin and PECAM-1 mRNA were documented. This work has shown the thiosemicarbazide derivative of captopril (8) as a potential anti-angiogenic agent targeting multiple factors in the angiogenesis of breast cancer cells. This study has demonstrated derivative (8) as a very promising molecule to be further investigated in other modes of angiogenesis and types of cancer. [ABSTRACT FROM AUTHOR]