Table 1.

Preclinical studies related to the implication of some relevant phytochemicals as antitumoral agents.

Natural Phytochemical	Dose	Preclinical Test	Target Mechanism	Target Gene	Reference
EGCG	0–50 µM	Colon cancer (HT-29 and HCT-116), human embryonic kidney (HEK)-293T cell, Triple negative breast cancer cells (MDA-231)	Apoptosis activation and reduction of cell proliferation via targeting MAPK	Akt, ERK1/2, p38	[56]
	0–200 µM	oral cancer (SSC5)	Reduce cell proliferation, activate apoptosis and autophagy	BAD, BAK, FAS, IGF1R, WNT11, ZEB1 CASP8, MYC, and TP53	[48]
	0–35 µM	Colorectal cancer cells (LoVo cells, SW480 cells, HT29 cells, and HCT-8 cells) and animal models	induced the apoptosis and affected the cell cycle via Notch signalling	HES1 and Notch2	[56]
	0–160 µM	Inflammatory breast cancer cells (UM-149 and SUM-190)	Inhibit tumoural stemm like comportment	VEGFD	[113]
	0–25 µM	Triple negative breast cancer cells	Invasion and angiogenesis	VEGFA	[45]
	0–50 µM	Breast cancer and nude mice	Cell proliferation and invasion	RS/MAPK/p-S6K1	[55]
	0–100 µM	Gastric cancer cells and nude mice	Cell proliferation, cell cycle, invasion and metastasis	Wnt/β-catenin	[114]
Morin	0–350 µM	human leukemic cells (U937 cells)	caspase-dependent apoptosis via intrinsic pathway	BAX, BCL-2, cytochrome c	[64]
	0–400 µM	human colon cancer cells (HCT-116)	ROS generation, extrinsic and intrinsic apoptosis	Bcl-2 and IAP family members, Fas and Akt	[64]
	0–200 µM	Triple negative breast cancer cells, nude mice	Cell adhesion, EMT, invasion and inhibit lung metastasis	TNF-α, VCAM1 and N-cadherin	[67]
	50 µM	Triple negative breast cancer cells, nude mice	EMT, invasion and metastasis	AKT and related targets, MMP-9	[66]
CAPE	0–100 µM	Breast cancer (MCF-7)	Activate apoptosis and reduce cell proliferation	NFkB, Fas, p53, Bax and JNK	[79]
	0–50 µM	Oral cancer cells (TW2.6)	Suppress the proliferation, invasion and metastatic potential	Akt and NFkB	[115]
	0–12 µM	Prostate cancer cells (PC-3)	suppresses the proliferation	70S6K and Akt	[116]
	0–50 µM	Prostate cancer cells (CRPC)	Cycle arrest and growth inhibition in CRPC cells	Skp2, p53, p21Cip1 and p27Kip1	[117]
Genistein	0–100 µM	breast cancer cells (MCF-7)	cell proliferation and apoptosis via IGF1R-Akt-Bcl-2 and Bax-mediated pathways	IGF-1R, p-Akt, Bcl-2, and Bax	[108]
	10 µmol/L	breast cancer cells (MCF-7)	Cell cycle regulation	GLIPR1, CDC20, BUB1, MCM2 and CCNB1	[109]
	0–50 µM	Colorectal cancer models and orthotopic mouse models	cell invasion and migration, inhibit distant metastasis	MMP-2 and FLT4	[110]
	0–100 µM	colon cancer cells (HCT-116)	Activate mitochondrial apoptosis	Akt and Bax	[107]
	0.5–10 μmol/L	Prostate cancer cells LAPC-4 and PC-3	Cell proliferation and hormonal receptor	ER-β	[106]
Kaempferol	25 μM	Breast cancer cells (MCF-7)	Modulated EMT, inhibit migration, and invasion	ER	[95]
	0–100 µM	Bladder cancer	Inhibit cell proliferation	c-Met/p38	[94]
	0–50 µM	Lung cancer cells (A549)	Modulated EMT, inhibit migration, and invasion	TGFβ1, SMAD3, Akt1	[96]
	0–100 µM	Oral cancer cells (SCC4)	anti-metastatic effect	MMP-2 and TIMP-2, c-JUN, and ERK1/2	[111]