Table 4.

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

Technological Platform	Cell Line and Treatment Conditions	Reported Mechanism	Other Conclusions	Reference
LD-microarray profiling expression of coding genes.	MCF-7 human breast adenocarcinoma (p53 wt/wt).	Resveratrol induced the intrinsic apoptosis pathway.	Changes in expression of some apoptosis-related genes were dependent on the concentration of curcumin: shifting in opposite directions at the low versus the high concentration. (This might suggest hormetic effects.)	[52]
		The activation of the p53-dependant apoptosis was evident by transcriptional up-regulation of CASP1, CASP2, CASP3, CASP4, BCL2L2, PIG3, and PIG11.
	Cells were incubated in media with 0, 25, or 50 μg/mL phytochemical (applied for 24 h).
		Observed changes also suggested indirect activation of apoptosis by down-regulation of pro-survival signals from growth factors and apoptosis inhibitors.
HD-microarray profiling expression of coding genes.	Hepatocellular carcinoma cell lines: KMCH, WRL68, Huh7, PLC, and Pitts1.	Curcumin indirectly promoted apoptosis by silencing pro-survival oncogenic signaling, in particular the NF-κB pathway.	Curcumin also modulated MYC signaling, which is known to have mixed effects (partially mitogenic and partially pro-apoptotic). Curcumin also modulated genes involved in cytokine signaling, growth factor signaling, and the regulation of angiogenesis.	[53]
	Cells were incubated with 25 μM phytochemical (applied for 72 h).
A microarray profiling microRNAs (miRCURY).	Several human cell lines originating from non-small cell lung cancers.	Resveratrol induced the intrinsic apoptosis pathway.	Altogether, six microRNAs were up regulated by the curcumin treatment: miR-132-3p, miR-183-5p, miR-124-3p, miR-215, miR-192-5p, and miR-194-5p. Moreover, two microRNAs were down regulated (i.e., miR-602 and miR-223-3p).	[54]
		The activation of the p53-dependant apoptosis was evident by up-regulation of pro-apoptotic miR-192-5p and miR-215.
		The microRNAs acts similarly to protein-coding anti-oncogenes inducing apoptosis in transformed cells. The induction of apoptosis involved the down-regulation of a known inhibitor of the intrinsic apoptosis pathway: X-linked inhibitor of apoptosis protein (XIAP—which normally binds and blocks initiator caspase 9). The resulting activation of the initiator caspase, in turn, led to the activation of effector caspases (in particular caspase-3) that rapidly effected cell death.
	Cells were incubated with 15 μM curcumin for 48 h.