Inhibition of Angiogenesis in Cancer Management by Antioxidants: Ascorbate and P. leucotomos
Pp. 132-146 (15)
Neena Philips, Halyna Siomyk, Hui Jia and Harit Parakandi
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.
Ascorbate, interleukin-8 (IL-8), matrixmetalloproteinases (MMPs), P.
leucotomos, transforming growth factor (TGF-β), Vascular endothelial growth
Professor of Biology, School of Natural Sciences, Fairleigh Dickinson University Teaneck, NJ 07666, USA.