Table 2.

Effect of polyphenols on the anti-cancer activity of etoposide—in vitro studies.

Polyphenol	In Vitro Model	Dose of Polyphenol	Dose of Etoposide	Interaction with Etoposide	Ref.
Apigenin	CCRF-CEM	LSD	LSD	ATP level ↑; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	Jurkat	LSD	LSD	ATP level ↑; caspase-3 and 9 activity ↑; level of cells in S phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	KG-1a	LSD	LSD	ATP level ↑; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑;	[29]
	THP-1	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
Catechin	MDA-MB-231	10–40 µM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
Curcumin	HL-60	20 µM	3–10 µM	apoptosis ↑; phosphorylation of the histone H2AX induced by etoposide ↑; ROS generation ↑	[30]
	SGC7901	1 mg	5 mg	cytotoxicity induced by etoposide ↑	[41]
	Weri-Rb1 and Y79	5–10 µM	0.1–20 µg/mL	etoposide-induced cytotoxicity ↑; level of apoptotic cells ↑; caspase 3 activity ↑; level of the cells in the G0/G1 phase of the cell cycle ↓	[43]
	LT12	1–20 µM	1–40 µM	level of cells arrested in the G2/M phase ↑; DNA damage ↑; number of apoptotic cells ↑	[47]
	MCF-7, HepG2, HCT116, HeLa	10 µg/mL	1 µg/mL	cytotoxicity of etoposide ↓; level of MCF-7 cells in S phase of cell cycle ↑; level of HCT116 and HeLa cells in the G2/M phase ↑;	[56]
	U-87MG	37.33 µg/mL (IC50)	6.5 µg/mL	cytotoxicity induced by etoposide ↑; BAX/Bcl-2 ratio ↑; expression of p10 and p53 ↓	[42]
	SGC7901	10–160 µM	2–200 µM	etoposide-induced cytotoxicity ↑; phosphorylation of IκBα ↓; level of apoptotic cells ↑; Bcl-2 and Bcl-xL expression ↓; attenuated the activation of NF-κB	[40]
Cyanidin	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
EGCG	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
	Ramos	7.5 µM	0.02 µg/mL	apoptosis induced by etoposide ↑	[38]
	MDA-MB-231 and T-47D	10 µM	0.1 µM	interferes with the formation of the anti-apoptotic GRP78-caspase-7 complex, which leads to an increase etoposide-induced apoptosis; suppresses the transformed phenotype of breast cancer cells treated with etoposide	[31]
Emodin	CCRF-CEM	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	Jurkat	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	KG-1a	LSD	LSD	caspase-9 activity ↑	[29]
	THP-1	LSD	LSD	caspase-9 activity ↑	[29]
Fisetin	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
	MG-63 and Saos-2	5–150 µM	0.5–10 µM	shows negative-to-positive interactions on the inhibition of cell proliferation depending on the relative concentrations; level of cells in G2-phase of the cell cycle ↑; cells in G1-phase ↓; levels of cyclins B1 and E1 ↓	[39]
Gossypol	Ramos	12 µM	20 µM	apoptosis in a time-dependent manner via activation of caspase-3 signaling ↑; enhances cytosolic cytochrome c release ↑	[37]
Genistein	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
	CEM	50 µM	0–200 µM	no impact on the cytotoxicity and genotoxicity induced by etoposide	[57]
Kaempferol	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
	HL-60	10–50 µg/mL	1 µM	DNA damage induced by etoposide ↑	[45]
	HL-60	10–50 µg/mL	1–10 µM	sensitivity of cells to etoposide ↑; ROS generation ↓	[46]
Naringenin	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
Quercetin	MDA-MB-231	10–40 μM	1 µM	inhibition of etoposide-induced Chk1 Ser345 phosphorylation	[44]
	HL-60	0.5–100 µM	1–10 µM	ROS generation ↓; apoptosis ↓	[58]
	LT12	1–20 µM	5 µM	oxidative DNA damage ↓	[59]
	HCT116	50 µM	50 µM	cyclin B1 level ↓; abrogates the increase in levels of p53 or its targets BAX and p21 induced by etoposide	[49]
	HSPCs	50 µM	10 µM	frequencies of MLL rearrangements in human HSPCs ↑	[52]
	CCRF-CEM	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	Jurkat	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	KG-1a	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; glutathione level ↓; γH2AX foci ↑	[29]
	THP-1	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S and G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
Resveratrol	WE-68, SK-ES-1 and SK-N-MC	5–10 µM	0.1–1 µM	etoposide-induced p21 expression in WE-68 cells ↓; etoposide-induced cell death ↓	[60]
	SCC25, CAL27 and FaDu	40 µM	10 µM	etoposide-induced apoptosis ↑	[36]
	HepG2, HCT-116	12.5–100 µM	1–10 µM	etoposide-induced p53 expression ↑; anti-proliferative effects of etoposide ↑	[35]
	HT-29	50–400 µM	100–500 µM	cell death induced by etoposide ↑; ROS generation ↑; chemosensitivity of cells ↑; AMPK ↑	[34]
	Cancer stem cells (CSC) from HeLa	137 µM	5.8 µg/mL	sensitizes cervical CSC cells to etoposide treatment by RAD51 inhibition	[33]
Rhamnetin	HepG2	3 µM	120 nM	level of cells in S phase of cell cycle ↑; IC50 value of etoposide ↓	[32]
Rhein	CCRF-CEM	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	Jurkat	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	KG-1a	LSD	LSD	caspase-9 activity ↑; glutathione level ↑	[29]
	THP-1	LSD	LSD	caspase-9 activity ↑; glutathione level ↑	[29]
cis-Stilbene	CCRF-CEM	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in S phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	Jurkat	LSD	LSD	ATP level ↓; caspase-3 and 9 activity ↑; level of cells in G2/M phase of cell cycle ↑; glutathione level ↓; γH2AX foci ↑	[29]
	KG-1a	LSD	LSD	caspase-9 activity ↑; glutathione level ↑	[29]
	THP-1	LSD	LSD	caspase-9 activity ↑; glutathione level ↑	[29]
Taurin	MCF-7, HepG2, U251, HeLaand HCT116	10–50 µg/mL	1 µg/mL	no effect on etoposide cytotoxicity	[56]

↑—increase; ↓—decrease; LSD—lowest significant dose.