Table 1.

Summary of the anticancer effects of tangeretin.

	Cell line	Function	Proposed mechanism of action	Reference
Ovarian cancer	OVCAR-3	Antiangiogenesis	Decrease in VEGF expression.	He et al. [53]
	A2780/CP70
	A2780/CP70	Cell cycle regulator	Caspase cascade, cell cycle arrest at G(2)-M phase.	Arafa et al. [31]
	2008/C13	Apoptosis inducer	Downregulation of phospho-Akt along with NF-KB, phospho-GSK-3beta, and phospho-BAD.
Gastric cancer	AGS	Apoptosis inducer	Reduction in the MMP.	Dong et al. [32]
			Upregulation of BAX with p53 activation.
Lung cancer	CL1-5	Apoptosis inducer	Decreasing expression of Bcl-2, XIAP, and survivin.	Li et al. [16]
			Disturbance in MMP.
			Translocation of cytochrome C to the cytosol.
	H1299	Antiproliferative	Inhibition of IL-1B-induced COX-2 expression.	Chen et al. [79]
	A549	Apoptosis inducer	Deactivation of NF-κB downstream.
Prostate cancer	PC-3	Antimetastatic	Downregulation of mesenchymal proteins.	Zhu et al. [80]
			Upregulation of epithelial proteins.
		Antiproliferative	Downregulation of PI3K/Akt/mTOR pathway.
Leukemia	MOLT-4	Reverse MDR	Inhibition of P-glycoprotein function.	Ishii et al. [81]
	K562/ADM	Reverse MDR	Inhibition of P-glycoprotein-mediated efflux of [(3)H]vincristine.	Ikegawa et al. [82]
	HL-60	Apoptosis inducer	Lowering DNA content.	Hirano et al. [45]
		Cell cycle regulator	Decrease of G1 cells, increase of S and/or G2/M cells.
	L1210	Antiproliferative	Inhibition of cell growth	Satoh et al. [83]
	K562
	JCS	Autophagy inducer	Increase in phagocytic activity of the cells.	Mak et al. [84]
Melanoma	B16F10	Melanogenesis	Increasing levels of tyrosinase, TRP-1, and ERK 1/2	Yoon et al. [85]
			Increasing expression of CREB and MITF
	JB6 P+	Anti-inflammatory	Blockage of Akt, MAPKs, and MAPK kinases.	Yoon et al. [86]
		Antioxidant	Scavenging ROS.
	B16F10	Antiproliferative	Inhibition of cell growth.	Rodriguez et al. [87]
	SK-MEL-1
	HTB43	Antiproliferative	Greater membrane uptake.	Kandaswami et al. [88]
				Kandaswami et al. [89]
Brain cancer	IOMM-Lee	Apoptosis inducer	Enhancing phosphorylation of GSK3β.	Das et al. [90]
	CH157 MN		Downregulation of TSPAN12, Bcl-XL, and Mcl-1.
			Overexpression of Bax and caspase-3.
	U-87MG	Cell cycle regulator	Increases G2/M arrest.	Ma et al. [91]
	LN-18	Apoptosis inducer	Modulating PTEN and cell-cycle regulated genes (cyclin-D and cdc-2 mRNA and protein expressions).
	Grade III astrocytoma	Antimetastatic	Downregulation of MMP-2 and MMP-9	Rooprai et al. [92]
Breast cancer	DMBA-induced rat mammary carcinoma	Antitumor	Decrease in levels of estradiol, progesterone, and prolactin.	Arivazhagan and Pillai [93]
		Antioxidant	Decrease in levels of LPSA, TSA, NO, and protein carbonyls.
		Antiproliferative	Reduction in PCNA, COX-2, and Ki-67 markers.
		Cell cycle regulator	Arresting cell division at the G1/S phase via p53/p21 upregulation.
		Antimetastatic	Downregulation of MMP-2, MMP-9, and VEGF.
	MCF-7/6	Immune-modulator	Reducing the number of NK cells.	Depypere et al. [94]
	MCF-7 MDA-MB-435	Antiproliferative	Blocking cell cycle progression at G1.	Morley et al. [42]
	MCF7 MDA-MB-468	Antiproliferative	Blocking cell cycle progression at G1.	Surichan et al. [12]
			CYP1A1/CYP1B1-mediated metabolism to 4′ hydroxy tangeretin.
	DMBA-induced mammary carcinoma	Antioxidant	Normalizing levels of AST, ALT, ALP, ACP, 5′-ND, γ-GT, and LDH.	Lakshmi and Subramanian [36]
			Decrease in TBARS, enzymatic, nonenzymatic antioxidants, phase I and phase II detoxification.	Periyasamy et al. [29]
	DMBA-induced mammary carcinoma	Antioxidant	Normalizing activities of glycolytic enzymes.	Periyasamy et al. [95]
			Increasing activities of citric acid cycle and respiratory chain enzyme.
		Antiproliferative	Downregulation of PCNA expression.
Liver cancer	HepG2	Antioxidant	Suppressing of TAG synthesis and mass.	Kurowska et al. [68]
			Decreasing activities of DAG acyltransferase and microsomal triglyceride transfer protein.
			Activating PPAR.
	REL	Antiproliferative	Upregulation of GJIC.	Chaumontet et al. [96]
				Chaumontet et al. [97]
Colorectal cancer	HT29	Cell cycle regulator	Arresting G2/M phase with reduction in ALDH+.	Silva et.al. [98]
	COLO 205	Cell cycle regulator	Blocking cell cycle progression at G1 phase.	Pan et al. [30]
		Antiproliferative	Inhibiting the activities of Cdk2 and Cdk4.
		Apoptosis inducer	Increasing in p21, p27, and p53 levels.