Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy

Table 1 Effect of Natural Compounds Targeting Major Stem Cell Signaling Pathways

Major signaling pathways	Compounds	Target	Effect	References
Notch	Curcumin	Downregulates transcription and translation Notch-1 and downstream genes Hes-1, Hey-1, and Hey-2 mRNA levels	¹Induces apoptosis by increasing reactive oxygen species	[43, 55]
Notch	Diallyl trisulfide	Targets Notch-1 intracellular domain	Decreases expression of Notch downstream genes. Increases expression of potential tumor suppressor micro RNAs (miR-143 and miR-145) and decreases tumor promoting micro RNA miR-21	[43, 55]
WNT/β-catenin	Resveratrol	β-catenin; histone H2AX	Apoptosis of OS cells by decreasing mRNA and protein expression of β-catenin and c-Myc Histone H2AX phosphorylation causes telomere instability and DNA damage	[24, 51, 54]
WNT/β-catenin	Apigenin	β-catenin	Decreases protein expression of β-catenin and decreases matrix metalloproteinase 14 (MMP14) expression	[24, 51, 54]
Hedgehog	Cyclopamine	Binds to SMO	Prevents signal transduction to GLIS	[30]
PI3/AKT	Sulforaphane	ERK and AKT	Suppresses ERK and AKT phosphorylation, induces apoptosisthrough G2/M phase arrest	[46]

ISSN: 1756-8722