Xenohormetic Phytochemicals Inhibit Neovascularization in Microphysiological Models of Vasculogenesis and Tumor Angiogenesis

Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlation...

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Bibliographic Details
Published in:	Advanced biology Vol. 8; no. 7; pp. e2300480 - n/a
Main Authors:	Kpeli, G. Wills, Conrad, K. Michael, Bralower, William, Byrne, C. Ethan, Boue, Stephen M., Burow, Matthew E., Mondrinos, Mark J.
Format:	Journal Article
Language:	English
Published:	Germany 01-07-2024
Subjects:	Angiogenesis Angiogenesis Inhibitors - pharmacology Cell Line, Tumor Citrus paradisi - chemistry Endothelial Cells - drug effects Endothelial Cells - metabolism Female Flavanones - pharmacology Glyceollin Glycine max - chemistry Human Umbilical Vein Endothelial Cells - drug effects Humans microphysiological systems Naringenin Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - prevention & control organ chips Phytochemicals Phytochemicals - pharmacology polyphenols Pterocarpans - pharmacology Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology tumor microenvironment vasculogenesis xenohormesis polyphenols Glyceollin vasculogenesis Naringenin Phytochemicals microphysiological systems angiogenesis xenohormesis tumor microenvironment organ chips
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Summary:	Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlations with human pathophysiology are lacking. Here, potent inhibitory effects of grapefruit‐derived Naringenin (Nar) and soybean‐derived Glyceollins (Gly) in human microphysiological models of bulk tissue vasculogenesis and tumor angiogenesis are reported. Despite this interference of vascular morphogenesis, Nar and Gly are not cytotoxic to endothelial cells and do not prevent cell cycle entry. The anti‐vasculogenic effects of Glyceollin are significantly more potent in sex‐matched female (XX) models. Nar and Gly do not decrease viability or expression of proangiogenic genes in triple negative breast cancer (TNBC) cell spheroids, suggesting that inhibition of sprouting angiogenesis by Nar and Gly in a MPS model of the (TNBC) microenvironment are mediated via direct effects in endothelial cells. The study supports further research of Naringenin and Glyceollin as health‐promoting agents with special attention to mechanisms of action in vascular endothelial cells and the role of biological sex, which can improve the understanding of dietary nutrition and the pharmacology of phytochemical preparations. Human microphysiological systems can help establish connections between known biochemical actions of xenohormetic phytochemicals and complex pathophysiological processes. This study demonstrates inhibition of bulk tissue vasculogenesis by grapefruit‐derived Naringenin and soybean‐derived Glyceollin and identifies a novel component of sex‐specificity in the phytochemical response. Inhibitory effects of the same phytochemicals in a model of tumor angiogenesis establish pathophysiological relevance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2701-0198 2701-0198
DOI:	10.1002/adbi.202300480