A paradox from a neurotransmitter: the opposite effects of substance P and its physiological fragments SP (1-7) and SP (9-11) on the proliferation of human breast cancer cells and the migration capabilities of HUVEC cells

Abstract

OBJECTIVE: Substance P (SP) is a neurotransmitter peptide, and it is known to play a major role in neurogenic inflammation, inducing local inflammatory responses, cancer, and angiogenesis. It has been previously demonstrated that SP possesses a wide range of pharmacological effects including induced cancer cell proliferation and triggered angiogenic response of tumors. However, there is no published work regarding the proliferative effects of its physiological fragments [N-terminal fragment SP (1-7) and C-terminal fragment SP (9-11)] not only on cancer cells but also on human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Cells were treated with different doses of fragments and the cytotoxic effects on the proliferation of MDA-MB-231 cells were determined via MTT kit (Promega, Madison, WI, USA) and Cellular DNA Fragmentation Elisa Kit (Roche). Changes both in the pro-angiogenic and anti-angiogenic factor levels in media were evaluated by; Human VEGF ELISA kit (Thermo-Scientific, Waltham, MA, USA), Human Matrix Metallo-proteinases-9 Elisa kit (Legend Max), and Human Thrombospondin-1 Elisa kit (R&D Systems) for VEGF, MMP-9, and Thrombospondin-1 respectively. To determine the changes in the migration capabilities of HUVECs, a wound healing test was performed. RESULTS: According to our results, the fragments exhibit different effects not only on the proliferation of cancer cells and the release of pro/anti-angiogenic factors from the cells but also on the migration capabilities of HUVECs. CONCLUSIONS: This is the first report showing that the SP fragments could behave differently from the main peptide itself.

Keywords

• substance p
• n-terminal fragment sp (1-7)
• c-terminal fragment sp (9-11)
• proliferation
• anti-angiogenesis