Table Info

Table 1.

Anticancer action of flavonoids mediated by different GPCRs

Subfamily of GPCRs	GPCR	Flavonoid	Cancer model	Molecular mechanisms of biological effects	Reference
Adrenoceptors	α_2C-AR	Quercetin (0.1 µM)	MCF-10A human mammary epithelial cells	[³H]-NA binding to α_2C-AR↓ 4-OHE₂- and NA-induced γ-H2AX and apurinic sites↓	[14]
	α_2C-AR	Quercetin-3-O-glucuronide (0.1 µM)	MCF-10A human mammary epithelial cells	[³H]-NA binding to α_2C-AR↓ 4-OHE₂- and NA-induced γ-H2AX and apurinic sites↓	[14]
	β₂-AR	Quercetin-3-O-glucuronide (0.1 µM)	MDA-MB-231 human breast adenocarcinoma cells	[³H]-NA to β₂-AR↓ NA-induced ROS/NF-κB↓, cAMP/PKA↓, MAPK↓, MMP-9↓ NA-induced invasion↓	[8]
Cannabinoid receptor	CB₁R	Quercetin (50 µM)	Caco2 human colon adenocarcinoma cells	CB₁R mRNA and protein expression↑ PI3K/Akt/mTOR↓, JNK/JUN↑ Cell growth↓, cell cycle progression from S to G2/M↓, apoptosis↑, cell migration↓	[15]
		Quercetin (50 µM)	DLD-1 human colon adenocarcinoma cells	CB₁R mRNA and protein expression↑ Cell growth↓	[15]
		Quercetin (0.5% of standard diet)	Intestinal tissue of AOM-treated C57BL/6J male mice	CB₁R mRNA and protein expression↑ STAT3↓, p-STAT3↓, Bax/Bcl-2↑	[22]
Chemokine receptor	CXCR4	Apigenin (20 µM, 40 µM)	Arsenic-transformed Beas-2B human bronchial epithelial cells (B-AsT)	CXCR4 protein expression↓ Constitutive and CXCL12-induced cell migration and invasion↓	[4]
		Apigenin (40 mg/kg)	B-AsT cells-injected male athymic nude mice	CXCR4 protein expression↓ Tumor growth↓	[4]
		Luteolin (10 µM, 30 µM)	MDA-MB-231 human breast carcinoma cells	CXCR4 mRNA and protein expression↓ Cell invasion↓	[21]
		Luteolin (40 mg/kg)	Lung tissue of B16F10 murine melanoma cells-injected C57BL/6 male mice	CXCR4 mRNA and protein expression↓ The number of lung metastases↓	[21]
		Fisetin (40 µM)	A549 human non-small cell lung cancer cells	CXCR4 mRNA expression↓ Apoptosis↑	[17]
		Myricetin (25 µM, 50 µM)	PC-3 human prostate cancer cells	Disruption of PIM1/CXCR4 interaction↑, CXCL12-CXCR4 axis↓ CXCL12-induced migration↓	[7]
		Myricetin (25 mg/kg)	PC-3 cells-injected athymic nude mice	Phosphorylated CXCR4 expression↓ Lung and bone metastasis↓	[7]
		Ampelopsin (25 µM, 50 µM)	PC-3 human androgen-independent prostate cancer cells	CXCR4 protein expression↓ Cell migration↓, cell invasion↓	[20]
		Ampelopsin (300 mg/kg)	Orthotopic PC-3 tumor model in male severe combined immunodeficient mice	CXCR4 protein expression↓ Lymph node metastases↓, lung metastases↓	[20]
		Xanthohumol (50 µM)	MDA-MB-231 human breast adenocarcinoma cells	CXCR4 mRNA and protein expression↓ CXCL12-induced invasion↓	[3]
		Xanthohumol (50 µM)	SW620 human colon adenocarcinoma cells	CXCR4 mRNA and protein expression↓ CXCL12-induced invasion↓	[3]
Membrane estrogen receptor	GPR30	Baicalein (8 µM)	MCF-10A and MCF-12A human mammary non-tumorigenic epithelial cells	E2-induced GPR30-mediated SRC, EGFR, ERK1/2 and Akt signaling↓ Tumorigenesis↓	[16]
		Baicalein (10 µM, 15 µM)	MCF-7 human breast cancer cells	E2-induced GPR30-mediated EGFR, ERK1/2 and Akt signaling↓, MMP-9 mRNA and protein expression and activity↓ E2-induced GPR30-mediated cell migration, adhesion, and invasion↓	[5, 6]
		Baicalein (10 µM, 15 µM)	SK-BR-3 human breast cancer cells	E2-induced GPR30-mediated EGFR, ERK1/2 and Akt signaling↓ E2-induced GPR30-mediated cell migration, adhesion, and invasion↓	[5]
Parathyroid HR	PTHR1	Quercetin (80 µM, 100 µM)	U2OS and Saos-2 human metastatic osteosarcoma cells	PTHR1 mRNA and protein expression↓ Cell proliferation↓, migration↓, adhesion↓, invasion↓	[9]
Prostanoid receptor	EP3R	Genistein (50 µM, 80 µM)	Human oral (MMel-1, MMel-2), uveal (OCM-1, OCM-3) and cutaneous (G361, WM-115) melanoma cells	EP3R mRNA expression↓ PGE2-induced and EP3R-mediated IL-8 mRNA expression↓ Cell proliferation↓	[18]

4-OHE₂: 4-hydroxyestradiol; Akt: protein kinase B; AOM: azoxymethane; AR: adrenoceptor; Bax: Bcl-2-associated X protein; Bcl-2: B cell lymphoma-2; cAMP: cyclic adenosine monophosphate; CB₁R: cannabinoid receptor 1; CXCL12: C-X-C motif chemokine ligand 12; CXCR4: C-X-C chemokine receptor type 4; E2: 17β-estradiol; EGFR: epidermal growth factor receptor; EP3R: prostaglandin E receptor 3; ERK1/2: extracellular signal-regulated kinases 1/2; GPCR: G protein-coupled receptor; HR: hormone receptor; IL-8: interleukin-8; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MMP-9: matrix metalloproteinase-9; mTOR: mammalian target of rapamycin; NA: noradrenaline; NF-κB: nuclear factor-κB; PGE2: prostaglandin E2; PI3K: phosphoinositide 3-kinase; PIM1: Moloney murine leukemia virus 1; PKA: protein kinase A; PTHR1: parathyroid hormone receptor 1; ROS: reactive oxygen species; SRC: proto-oncogene tyrosine-protein kinase Src; STAT3: signal transducer and activator of transcription 3

Declarations

Author contributions

KS: Conceptualization, Investigation, Methodology, Visualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

Katrin Sak who is the guest editor of the special issue “Molecular Mechanisms and Intervention Options in Metastatic Spread of Cancer” of Exploration of Targeted Anti-tumor Therapy had no involvement in the decision-making or the review process of this manuscript.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent of publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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