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


Koçak O., ŞİMŞEK E.

World Cancer Research Journal, cilt.9, 2022 (ESCI) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 9
  • Basım Tarihi: 2022
  • Doi Numarası: 10.32113/wcrj_20221_2163
  • Dergi Adı: World Cancer Research Journal
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus
  • Anahtar Kelimeler: Anti-Angiogenesis, C-terminal Fragment SP (9-11), N-terminal Fragment SP (1-7), Proliferation, Substance P
  • Akdeniz Üniversitesi Adresli: Evet

Özet

© 2022, Verduci International. All rights reserved.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.