Table 3.

Studies on the ability of Citrus flavonoids to inhibit tumor development.

Promotion Phase
Flavonoid	Concentration/Dose	Experimental Model	Reference
Quercetin, taxifolin, nobiletin, tangeretin	2–8 μg/mL	HTB43 cells	[48]
Tangeretin	50–100 μM	HL-60 cells	[49]
Tangeretin	2.7–27 μM	HL-60 cells	[50]
Tangeretin, nobiletin	54 μM (tangeretin)	MDA-MB-435, MCF-7, and HT-29 cells	[51]
	100–200 μM for MDA-MB-435
	60 μM for MCF-7
	200 μM for HT-29 (nobiletin)
Tangeretin	10–50 μM	COLO 205 cells	[52]
Nobiletin	20–200 μM	TMK-1, MKN-45, MKN-74, and KATO-III cells	[53]
Tangeretin	10−7–10−4 M	T47D cells	[56]
Nobiletin	20–30 μM	H2O2-treated SH-SY5Y cells	[57]
Tangeretin, nobiletin	IC50 4 mg/mL	Brain tumor cells	[58]
Tangeretin	150 μM	A2780/CP70 and 2008/C13 cells	[59]
Tangeretin	5–240 μM	AGS cells	[60]
Nobiletin	1 × 10−7–5 × 10−4 mol/L	TRAP rats	[61]
Nobiletin	0.05%	PhIP-treated rats	[62]
Nobiletin	0.01%–0.05%	AOM-treated rats	[63]
Chrysin, quercetin, nobiletin	100 ppm	AOM-treated mice	[64]
Nobiletin	100 ppm	AOM/DSS-treated mice	[65]
Nobiletin	1.25–80 μM	A549 cells	[66]
Nobiletin	10−3 M	MH1C1 and HepG2 cells	[67]
Nobiletin	10–100 μM	C6 cells	[68]
Nobiletin	20–100 μM	U87 and Hs683 cells	[69]
Nobiletin	0–200 μM	AGS, MKN-45, SNU-1, and SNU-16 cells	[70]
Nobiletin	0–160 μM	HL-60, U937, THP-1, OCI-AML3, and MV4-11 cells	[71]
Nobiletin	0.05 wt%	AOM/DSS-treated CD-1 mice	[72]
Apigenin	1–100 μM	MDA-MB-453 cells	[73]
Apigenin	0–40 μM	MCF-7, MCF-7 HER2, SK-BR-3 cells	[74]
Apigenin	10–70 μM	MDA-MB-453, BT-474, SKBr-3, MCF-7, and HBL-100 cells	[75]
Apigenin	0–60 μM	HT-29 and MG63 cells	[77]
Apigenin	10–50 μM	HDF cells	[78]
Apigenin	IC50: 7.8 μg/mL for MCF-7 and 8.9 μg/mL for MDA-MB-468 cells	MCF-7 and MDA-MB-468 cells	[80]
Apigenin	1–100 μM	BxPC-3 and MiaPaCa-2 cells	[81]
Apigenin	6.25–100 μM	AsPC-1, CD18, MIA PaCa2, and S2-013 cells	[82]
Apigenin	10–100 μM	BxPC-3 and PANC-1 cells	[83]
Apigenin	10–80 μM	LNCaP cells	[84]
Apigenin	1–20 μM	DU145 cells	[85]
Apigenin	0–80 μM	SW480, HT-29, and Caco-2 cells	[86]
Apigenin	10–10 μM	HCT-116, SW480, HT-29, and LoVo cells	[87]
Apigenin	20–50 μg/mouse	22Rv1 and PC-3 cells-implanted mice	[88]
Apigenin	50 μM	SH-SY5Y cells	[89]
Apigenin	15–60 μM and 25 mg/kg	NUB-7, LAN-5, and SK-N-BE cells and NUB-7 inoculated xenograft mice	[90]
Flavonids	25–250 μM	HT-29, Caco-2, LLC-PK1, and MCF-7 cells	[92]
Diosmin	0–120 μM and 15 mg/kg	HA22T cells and HA22T xenograft mice	[93]
Diosmin	50–250 μM	DU145 cells	[94]
Diosmin, hesperidin	1000 ppm	MNAN-injected rats	[95]
Diosmin, hesperidin	1000 ppm	4-NQO-exposed rats	[96]
Diosmin, hesperidin	500–1000 ppm	OH-BBN-exposed rats	[97]
Diosmin, hesperidin	1000 ppm	AOM-injected rats	[98]
22 flavonoids	0–10 μM	HL-60, A431, SK-OV-3, HeLa, HOS cells	[99]
Quercetin	0–100 μM	Caco-2 and HT-29 and IEC-6 cells	[102]
Quercetin	0–50 μM	Prostate and skin cells	[104]
Quercetin	0–50 μM	MDA-MB-231, MDA-MB-453, AU565, BT483, BT474, and MCF-7 cells	[105]
Quercetin	0–10 μM	SK-Br-3 and SK-Br-3-Lap R cells	[106]
Quercetin	2.5–40 μM	MDA-MB-231, MCF-7, and MCF-10A cells	[107]
Quercetin	1–10 μM	MCF-7ADR-resistant cells	[108]
Naringenin	0–1 mM	HL-60 cells	[110]
Naringenin	0.02–2.85 mmol	HT-29 cells	[112]
Naringenin	10 μM	MCF-7 cells	[113]
Naringenin	0–400 μM	THP-1 cells	[114]
Naringenin	50–750 μM	HaCaT and A431 cells	[116]
Naringenin	0.1–0.5 mM	HL-60 cells	[117]
Naringenin	100 μM	A549, H460, and WI-38 cells	[118]
Naringenin, hesperetin, apigenin	50 μM	MCF-7 and NCI-H460 cells	[119]
Naringenin, kaempferol	25–100 μM	HK-2 cells	[121]
Naringenin	10 mg/kg	Rats	[122]
Naringenin, naringin	0.7 mg/kg (naringenin) and 2.4–9.4 mg/kg (naringin)	Rats	[123]
Naringenin	100 μM	A549, MCF-7, HepG2, and MCF-7/DOX cells	[124]
Naringin, naringenin, quercetin	50 mg/kg (naringin or naringenin) and 100 mg/kg (quercetin)	Rats	[125]
Naringenin	200 mg/kg	MNNG-treated rats	[126]
Naringenin	200 mg/kg	MNNG-treated rats	[127]
Naringenin	50 mg/kg	C6 cells-injected rats	[128]
Naringin, naringenin	2.5%	Hamsters	[129]
Naringin	250–2000 μM	SiHa cells	[130]
Naringin	1000 μmol/L	HeLa cells	[131]
Naringin	0–3200 μM	HeLa and A549 cells	[132]
Naringin	50–200 μM and 100 mg/kg	MDA-MB-231, MDA-MB-468, and BT-549 cells/MDA-MB-231 xenograft mice	[133]
Naringin	0–150 μM	5637 and T24 cells	[134]
Naringin	1.2–3 mM	AGS cells	[137]
Naringin	50–200 μM	MDA-MB-231, MDA-MB-468, and BT-549 cells	[138]
Naringin	200 mg/kg	AOM-injected rats	[139]
Naringin	10.25–35 mg/kg	W256 rats	[140]
Naringin	150 mg/kg	Apc(Min/+) mice	[141]
Hesperetin, hesperidin, naringenin, naringin	40–80 μM	HL-60, THP-1, and PMN cells	[143]
Hesperetin	0–200 μM	MCF-7 cells	[144]
Hesperetin	5–100 μM	HT-29 cells	[145]
Hesperetin	0–125 μmol/L	BON cells	[146]
Hesperetin	125–1000 μM	SiHa cells	[147]
Hesperetin	0–600 μM and 10–40 mg/kg	HepG-2, SMMC-7721, and Huh-7/hepatocellular carcinoma xenograft mice	[148]
Hesperetin	20 mg/kg	DMH-injected rats	[149]
Hesperidin, hesperitin, rutin, neohesperidin	25–100 μg/mL	Panc-28 cells	[151]
Hesperidin	1–100 μM	SNU-C4 cells	[152]
Hesperidin	0–200 μM	HepG2 cells	[153]
Hesperidin	0.1–2 mM	HepG2 cells	[154]
Hesperidin	0–100 μM	Ramos cells	[155]
Hesperidin	10–100 μM	NALM-6 cells	[156]
Hesperetin	0–200 μM	MCF-7, MCF-10A, HMEC and MDA-MB-231 cells	[157]
Hesperidin	20–100 μM	MCF-7 cells	[158]
Hesperidin	0–100 μM	HeLa cells	[159]
Hesperidin	0.32–32 μM	Caco-2, CCRF-CEM and CEM/ADR5000 cells	[160]
Hesperetin, quercetin	30 μM	K562, K562/BCRP, MCF7/WT, and MCF7/MR cells	[161]
Hesperidin	0–100 μM	MCF-7, LNCaP, PC-3 and DU-145 cells	[162]
Hesperidin	500 ppm	4-NQO-treated rats	[163]
Hesperidin	1%	DMBA/TPA-treated mice	[164]
Hesperetin	20 mg/kg	DMH-treated rats	[166]
Hesperetin	10–50 mg/kg	DMBA-treated rats	[167]
Hesperidin	25 mg/kg	BP-exposed mice	[168]
Hesperetin	1000–5000 ppm	MCF-7 xenograft mice	[169]
Didymin	0–20 μM	A549 and H460 cells	[170]
Poncirin	50–200 μM	AGS cells	[171]

4-NQO: 4-nitroquinoline 1-oxide; AOM: azoxymethane; DMH: 1,2-dimethylhydrazine; DSS: dextran sulfate sodium; MNAN: N-methyl-N-amylnitrosamine; MNNG: N-methyl-N′-nitro-N-nitrosoguanidine OH-BBN: N-butyl-N-(4-hydroxybutyl)nitrosamine; PhIP: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.