Natural Compounds Modulating Mitochondrial Functions

Table 2

Direct and in direct effects of Qu, RSV, and Cur on mitochondria-mediated apoptosis.

Molecule	Effects on mitochondrial-mediated apoptosis	Model used	Doses tested	Time of treatment	References
Quercetin
Direct proapoptotic effect	Loss of MMP, followed by release of cyt c	U937 cells; MDA-MB-231 cells	0–300 μM	Up to 24 hours	[106, 108]
	Inhibition of ANT and opening of PTP, followed by release of cyt c	Isolated mitochondria from rat kidney	0–50 μM	Up to 10 minutes	[38]
	Depletion of GSH, followed by loss of MMP and cyt c release	U937 cells, human peripheral blood mononuclear cells	0–100 μM	Up to 24 hours	[11, 112]
Indirect proapoptotic effects	Upregulation of Bax and Bak and downregulation of Bcl-2 and Bcl-xL	HepG2 cells	0–200 μM	Up to 72 hours	[108, 110]
	Activation of AMPK1/ASK1/p38 pathway through ROS increase	MCF-7 breast cancer cells; HCT116 and HT-29 cells	0–400 μM	Up to 24 hours	[109–111]
Resveratrol
Direct proapoptotic effects	Loss of MMP, opening of PTP, and release of cyt c	MCF-7, MDA-MB-231 cells, and HepG2 cells	0–200 μM	Up to 48 hours	[125, 126]
Indirect proapoptotic effects	Upregulation of p21 mediated by p53	Neuroblastoma (SHEP, GIMEN, and LAN5), medulloblastoma (PSFK), glioblastoma (U373MG, A172), melanoma (SK-Mel, Colo38), pancreatic (MiaPaCa2), prostate (LNCaP), and breast carcinoma (MCF-7) cells	0–100 μM	Up to 24 hours	[127]
	Downregulation of Bcl-xL, Mcl-1, and Bcl-2	Ramos and Raji, TIB-196 and CCL-155 B cell lines	0–200 μM	Up to 24 hours	[128, 129]
	Upregulation and oligomerization of Bax	HCT116 cells; F344 rats	0–100 μM; 200 μg/kg body wt/day	32 hours; three months	[131, 132]
Curcumin
Direct proapoptotic effects	Increase of , followed by increase in mitochondrial permeability and release of cyt c	HCT-116 and HT-29 cells	0–160 μM	Up to 72 hours	[140]
	PTP opening, followed by mitochondrial swelling and increase in permeability	Isolated mitochondria from rat liver	0–20 μM	Up to 15 minutes	[141]
	Release of cyt c and AIF	T98G, PC3, LNCaP, MDA-MB23, Jurkat cells, and immortalized human fibroblasts	15–25 μM	Up to 24 hours	[142, 143]
Indirect proapoptotic effects	Upregulation of Bax via a p53-dependent pathway	MCF-7 cells	10 μM	Up to 48 hours	[145]
	Upregulation of Bax, Bak, Bim, Bid, and Apaf-1	HCT-116, PC3, LNCaP, MDA-MB23, Jurkat cells, immortalized human fibroblasts, and embryonic fibroblasts	0–50 μM	Up to 72 hours	[143, 146, 147]
	Downregulation of Bcl-2 and Bcl-XL	HepG2, U266, and MM.1 cells	0–50 μM	Up to 16 hours	[137, 148]
	Damage of mtDNA, which impairs mitochondrial functions	HepG2, HT1080, and HEK293T cells	0–40 μM	Up to 24 hours	[135, 136]