Table 3.

There is strong evidence for the activation of the intrinsic apoptosis pathway by resveratrol.

Technological Platform	Cell Line and Treatment Conditions	Reported Mechanism	Other Conclusions	Reference
LD-microarray profiling expression of coding genes.	LNCaP human prostate adenocarcinoma cells (androgen-sensitive, p53 wt/wt).	Resveratrol induced the intrinsic apoptosis pathway (but only at the highest concentration tested).	At intermediate concentrations, resveratrol modulated cell cycle regulatory genes, and down-regulated markers of cellular proliferation. (At the lowest concentrations, resveratrol stimulated viability suggesting a hormetic response curve.)	[47]
	The phytochemical was applied in cell media in increasing concentrations: 0.01, 0.1, 1, 10, 25, 40, and 100 μM.	The activation of p53-dependant apoptosis was evident by the transcriptional upregulation of p21 and MDM2.	Resveratrol also had a strong inhibitory effect on the androgen pathway (which included prostate-specific antigen—PSA).
HD-microarray profiling expression of coding genes.	The following human lung cancer cells were used: NCI H460 (p53 wt/wt), NCI H23 (with a homozygous missense mutation: methionine to isoleucine at codon 246), and A549 (p53 wt/wt).	Resveratrol induced the intrinsic apoptosis pathway in wild-type A549 cells.	Resveratrol also inhibited growth of the p53 mutated cancer cell line (NCI H23) suggesting that it can also induce p53-independent apoptosis or cell cycle arrest.	[48]
	25 μM phytochemical was applied in cell media (with the incubation time of 48 h).	The activation of p53-dependant apoptosis was evident by transcriptional upregulation of p21 and p27.
	Human fibrosarcoma cells: HT1080 (p53 wt/wt).	Resveratrol induced the intrinsic apoptosis pathway.	Resveratrol also modulated the expression of genes associated with cell cycle, cytoskeleton, and cell-adhesion.	[49]
	The phytochemical was applied at 2195 ng/mL in media (with the incubation time of six hours).	The activation of p53-dependant apoptosis was evident by differential regulation of 13 genes in the KEGG’s p53 signaling pathway.
	MDA-MB-231 human breast cancer cell line (estrogen receptor negative).	Resveratrol induced the intrinsic apoptosis pathway.	There was also evidence for cell cycle arrest (increased fraction of cells in the G1 phase and inhibition of the expression of cyclin B1).	[50]
	10 μM phytochemical was applied in cell media (with the incubation time of six hours).	The activation of the p53-dependant apoptosis was evident by transcriptional upregulation of p21, PIG3, and BAD.
	Human renal carcinoma cells of likely proximal tubule origin. (These cells are known to have a p53 wt/wt genotype, but p53 signaling is strongly repressed.)	Resveratrol induced the intrinsic apoptosis pathway.	Fifteen-fold induction of tumor necrosis factor α inducible protein 3 (TNFAIP3) also suggested the induction of the extrinsic apoptosis pathway.	[51]
	50 μM phytochemical was applied in cell media (with the incubation time of 24 h).	The activation of the p53-dependant apoptosis was evident by sevenfold transcriptional upregulation of MDM2.