Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy

Table 2

Summary of anticancer mechanism of action of different flavonoids and their results in different cancer cell lines.

Flavonoids	Mechanism of action	Cell lines	Results	References
Quercetin	Quercetin inhibited Akt/PI3 K and MEK-ERK signaling while it augmented UVB-induced nuclear translocation of NF-κb.	Melanoma (B16-F10)	Minimal dosages of quercetin (10–20 M) induce apoptosis in UVB-irradiated melanoma cells via increasing reactive oxygen species (ROS), disrupting calcium homeostasis, and modulating antioxidant defenses	[98]
Apigenin luteolin, resveratrol, and EGC-3-gallate	The investigated compounds cause intracellular copper mobilization and ROS production, resulting in cancer cell death.	Breast cancer (MDA-MB-468), prostate cancer (PC3), pancreatic cancer (BxPC-3)	The investigated compounds cause intracellular copper mobilization and ROS production, resulting in cancer cell death	[99]
Silibinin	Silibinin triggered the MAP2K1/2-MAPK1/3 pathway but blocked the PI3/AKT/mTOR pathway.	Colorectal cancer (SW480)	Silibinin exacerbated oxidative stress in SW480 cells rapidly due to mixed phenotypes of ROS-induced apoptosis and autophagy	[100]
EGC analogs JP8	JP8 causes type I/II cell death in cancer cells by boosting ROS production and activating stress-related proteins like p-eIF2a, IREI, and CHOP.	Melanoma (B16-F10)	In B16-F10 melanoma murine cells, JP8 promotes autophagy and apoptosis but not in normal cells.	[101]
Curcumin (monocarbonyl analogs)	Compound A1 transforms TrxR antioxidant enzymes into a ROS promoter and causes an intracellular ROS explosion. Apoptosis is linked to the formation of reactive oxygen species.	Lung cancer (A549)	Mechanisms of cytotoxicity and proapoptosis	[102]
RWP (red wine polyphenols)	The mechanism of RWP included the suppression of PI3K/Akt kinase signaling, which was independent of its antioxidant potential.	Osteosarcoma (U20s)	RWP caused type I/II mixed cell death in a dose-dependent manner, with the highest effect occurring between 100 and 200 μg/ml equivalents of gallic acid	[103]
Novel synthetic polyphenol conjugate (DPP 23)	In transformed cells, DPP 23 preferentially activates the UPR in the endoplasmic reticulum via ROS production and caspase-dependent death.	Glioblastoma, pancreatic, beast, hepatocellular cancer cell lines	DPP 23 causes cancer cell lines to produce more ROS and activate apoptosis while having no impact on healthy cells	[104]
Tetrahydroxy-trans-stilbene derivatives	Oxidative damage, reduction of mRNA expression and superoxide dismutase activity, reduction of mitochondrial capacity, and glutathione depletion were all associated with cell death.	T cell leukemia (Jurkat cells)	Enhanced caspase 3 and 9 expression and cytotoxic activities	[105]