Inhibition of Angiogenesis in Cancer Management by Antioxidants: Ascorbate and P. leucotomos

The hallmarks of cancer include cell growth and metastasis, facilitated by angiogenesis and the remodeling of the extracellular matrix (ECM) by vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), transforming growth factor (TGF-β) and matrixmetalloproteinases (MMPs), which are the predominant factors. These factors are secreted by tumors or the stromal cells in the tumor niche. Oxidative stress and inflammation are the primary causes of the pro-angiogenic factors, including VEGF, MMPs, TGF-β, and IL-8 that collectively activate several signal transduction pathways such as MAP kinase and NF-kB to accentuate ECM remodeling, angiogenesis and cancer metastasis.

Ascorbate (Vitamin C) is a major regulator of the ECM and regulates cancer biology. It inhibits the invasiveness of several cancers such as gastric, oral, pulmonary, fibrosarcoma and melanoma. We have reported ascorbate’s dose-dependent inverse effects on cancer cell growth and the expression MMPs and TGF-β. An extract from P. leucotomos (a fern) in combination with ascorbate simultaneously reduces cancer cell growth as well as the expression of MMP-1 and TGF-β. Further, ascorbate and P. leucotomos, independently and in combination, inhibit the expression of VEGF in a dose dependent manner. A combination of ascorbate and P. leucotomos would benefit as preventive measure; and well as a supplemental regimen for cancer patients.

Keywords: Ascorbate, interleukin-8 (IL-8), matrixmetalloproteinases (MMPs), P. leucotomos, transforming growth factor (TGF-β), Vascular endothelial growth factor (VEGF).