. 2021 Feb 19;26(4):1109. doi: 10.3390/molecules26041109

Table 1.

Relevant in vitro studies, based on natural compounds with antitumor properties, subsequently correlated with in vivo studies and clinical trials.

Natural Compound	Cancer Type	Cell Line (s)	Active Concentrations	Findings	Cell Death Type	Ref.
Resveratrol	Breast cancer	4T1	IC₅₀ = 93 µM (72 h)	Cell cycle inhibition; S-phase arrest; ↑ cell apoptosis rate	Apoptosis	[60]
	Osteosarcoma	MNNG/HOS	IC₅₀ = 20.57 μM (48 h)	Cleavage of PARP, and caspase-3; ↑ Bax; ↓ Bcl-2 and Bcl-xL; JAK2/STAT3 pathway inhibition	Apoptosis	[61]
	Osteosarcoma	MG-63	IC₅₀ = 28.56 μM (48 h)		Apoptosis	[61]
	Cervical cancer	HeLa	IC₅₀ = 188 ± 19 µM (48 h)	↑ content of LAMP1, Atg7, LC3B, PINK1 and PARK2 proteins; ROS overload; ↓ glycolysis; ↓ oxidative phosphorylation protein contents and fluxes	Autophagy	[62]
	Colorectal cancer	SW480	5 µM	inducing cell cluster formation; ↓ cell viability	Apoptosis	[63]
	Colorectal cancer	HCT116	5 µM	inducing cell cluster formation; ↓ cell viability	Apoptosis	[63]
Curcumin	Melanoma	A375	IC₅₀ = 25 µM (24 h)	inhibition of cell invasion; G2/M phase cell-cycle arrest; suppression of the AKT, mTOR and P70S6K activation	Autophagy	[64]
	Melanoma	C8161	IC₅₀ = 15 µM (24 h)		Autophagy	[64]
	Breast Cancer	MCF-7	1–25 μg/mL (72 h)	↓ phosphorylation of Akt and MAPK; ↓ HER-2 oncoprotein; ↓ NF-κB	-	[65]
		MDA-MB-231
		BT-474
		SK-BR-3-hr
	Cervical Cancer	HeLa	12–14 µM (48 h)	DNA damage and fragmentation; chromatin condensation; ↑ amounts of p-ATM, p-ATR, p53, MDM2, BRCA1, DNA-PK, MDC1 and p-H2A.X, PARP and MGMT proteins	Apoptosis	[66]
	Colon Cancer	SW480	1–50 µM (24 h)	inhibition of the cellular invasive activity; ↓ uPA and MMP9 expression; ↓ NF-κB activation	-	[67]
	Colon Cancer	LoVo	1–50 µM (24 h)		-	[67]
EGCG	Colorectal Cancer	DLD-1	20–60 µM	↓ number and size of cell sphe-roids;inhibition of the Wnt/β-catenin pathway; ↓ pro-tein levels of Cyclin D1 and PCNA; ↓ Bcl-2; ↑ Bax, Caspase-8, Caspase-9, and Caspase-3	Apoptosis	[68]
	Colorectal Cancer	SW480	20–60 µM		Apoptosis	[68]
	Lung Cancer	A549	IC₅₀ = 36.0 μM (72 h)	↓ survival rate; loss of the adhe-sion ability; ↓ Bcl-xL	Apoptosis	[69]
	Breast Cancer	MDA-MB-231	≥ 75 μM (24 h)	↓ expression of β-catenin, p-Akt, and cyclin D1; inactivation of the β catenin signaling pathway; ↓ cell proliferation; disrupted adherence junction formation	-	[70]
Quercetin	Pancreatic Cancer	LNCaP DU-145 PC-3	40 μM (24, 48, and 72 h)	modulation of ROS production and mitochondrial membrane potential; interference with MAPK, Akt, and NF-κB signaling pathways	Apoptosis Necrosis	[38]
Quercetin	Cervical Cancer	HeLa	EC50 = 100 μM (24 h)	↑ expression of caspases and pro-apoptotic genes; DNA fragmentation; ↓ cell migration; G2-M cell cycle arrest; blockage of the PI3K, MAPK and WNT pathways	Apoptosis	[37]
	Colorectal Adenocarcinoma	Caco-2	IC50 = 35 μM (24 h)	NF-κB pathway inhibition; ↑Bax; ↓Bcl-2 increased cell membrane permeability; nuclear condensation	Apoptosis	[71]
Rutin	Colon Cancer	HT-29	100 and 200 μM (24 h)	↑ cleaved caspases-3, -8 and -9; ↓ Bcl 2; ↑ Bax; cell shrinkage; chromatin condensation; rounding, blebbing and an increased density of apoptotic bodies	Apoptosis	[72]
Betulinic acid	Melanoma	B164A5	10 mM	G0/G1 cell cycle arrest; ↓ cell proliferation	Apoptosis	[46]
	Ovarian Cancer	A2780	IC50 = 44.47 μM (24 h)	↑ levels of cleaved caspase-8, -3, -9; ↑ Bax; ↓ Bcl-2; nuclear Condensation	Apoptosis	[73]
	Colon Cancer	HCT116 SW480 DLD-1	≥ 5 µg/mL (48 and 72 h)	↑ Bax; ↑ cleaved caspase-3; ↑ ROS production; ↓ Bcl-2; ↓ mitochondrial membrane potential	Apoptosis	[74]
Artemisinin (Artesunate)	Breast Cancer	MDA-MB-231	25, 50 and 100 μM (48 h)	↓ Bcl-2; ↑ Bax; G2/M-phase arrest; ↓ Cyclin-B1 and Cyclin-D1; agglutinated heterochromatin; degenerated mitochondrial vacuoles; nuclear swelling; ↓ number of intracellular organelles	Apoptosis Autophagy	[50]
	Colon Cancer	HCT116	40 and 80 μM (24, 48, and 72 h)	Cell elongation; membrane foaming; nuclear condensation and fragmentation; chromatin shrinkage; ↓ Bcl 2 and Bcl xL; ↑ Bax; ↑ cleaved procaspase-3 to active caspase-3; ↑ levels of beclin 1, LC3 I/II, and Atg5; ↑ complexation of Atg12-Atg5	Apoptosis Autophagy	[51]
	Cervical Cancer	ME-180	300 and 500 μM (48 and 72 h)	↓ Telomerase activity; ↓ hTERT and hTR expression; ↓ E6 and E7 oncogenes; chromatin condensation; ↑ p53 expression	Apoptosis	[75]
Ginseng extract	Breast Cancer	MCF-7	100–400 μM (24 h)	↓ Bcl-2; ↑ Bax, cytochrome c, and cleaved caspase-3; ↑ ROS production	Apoptosis	[55]
Ginseng extract	Lung Cancer	A549	50–100 μM (48 and 72 h)	Punctate cytoplasmic expression of LC3, Beclin-1 and ATG5; G2/M phase arrest; ↑ expression of LC3-II; ↑ p-Akt; ↓ mTOR-4EBP1	Autophagy	[56]