Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

Table 1

Anticarcinogenic activity of citrus polymethoxyflavonoids and their derivatives.

Polymethoxyflavone	Functions	Mechanisms	References
Naringin	Cell cycle arrest	G1 cycle arrest by increasing p21 and decreasing survivin in MDA-MB-231 xenograft mice	[25]
	Anticancer metastasis	Suppressed the upregulation of metallopeptidase-9 (MMP-9) and repressed the PI3K/AKT/mTOR/p70S6K signaling pathway	[36]
Hesperetin	Cell cycle arrest	G1-phase cell cycle arrest in human breast cancer MCF-7 cells by downregulating CDK2 and CDK4 together with cyclin D and upregulating p21^Cip1 and p27^Kip1	[19]
		Induced the G2/M phase and increased expression of caspase-3, caspase-8, caspase-9, p53, Bax, and Fas death receptor and its adaptor protein Fas-associated death domain-containing protein (FADD) in human cervical cancer SiHa cells	[20]
	Suppress proliferation	Exerted significant inhibitory effect on proliferating cell nuclear antigen in ACF in 1,2-dimethylhydrazine induced colon cancer model in rats	[33]
		Inhibited growth of aromatase-expressing MCF-7 tumor in ovariectomized athymic mice by reducing cyclin D1, CDK4, and Bcl-x(L), while upregulating the level of p57^Kip2	[34]
Nobiletin	Cell cycle arrest	Blocked cell cycle progression at G1 breast cancer cell lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29	[22]
	Antiangiogenesis	Inhibited angiogenic differentiation induced by VEGF and FGF by downregulation of ERK1/2 and c-JNK and activation of the caspase pathway	[42, 44]
Tangeretin	Cell cycle arrest	Blocked cell cycle progression at G1 breast cancer cell lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29	[22]
	Suppress proliferation	Led to caspase-3 activation and elevated surface phosphatidylserine in human cocon LoVo/Dx cells	[28]
	Anticancer metastasis	Inhibited PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation	[38]
	Scavenging of ROS	Inhibited cancer cell proliferation by SOD, CAT, GPx, and nonenzymatic antioxidants and phase II detoxification in 7,12-dimethyl benz(a)anthracene induced mammary carcinoma in rats	[45]
5-Demethyltangeretin (5DT)	Cell cycle arrest	Upregulated p53 and p21^Cip1/Waf1 and downregulated cdc-2 and cyclin B1 leading to G2/M cell cycle arrest	[23]
Sinensetin	Antiangiogenesis	Inhibited angiogenesis by inducing cell cycle arrest in the G0/G1 phase in HUVEC culture; in zebrafish embryos, it downregulated the mRNA expressions of angiogenesis genes flt1, kdrl, and hras	[43]
5HTMF	Suppress proliferation	Induced cellular apoptosis in human colon cancer cells by p53- and Bax-dependent mechanisms in HCT116 colon cancer cells	[24]
	Cell cycle arrest	Induced cell cycle arrest at G0/G1 phase through a p53- and p21^Cip1/Waf-dependent mechanism in HCT116 colon cancer cells	[24]
5HPMF	Suppress proliferation	Induced cellular apoptosis in human colon cancer cells by p53- and Bax-dependent mechanisms in HCT116 colon cancer cells	[24]
5HHMF	Cell cycle arrest	Induced G2/M arrest through p53- and p21-independent mechanisms in HCT116 colon cancer cells	[24]
	Suppress proliferation	Induced cellular apoptosis in human colon cancer cells by p53- and Bax-dependent mechanisms in HCT116 colon cancer cells	[24]
Naringenin	Cell cycle arrest	Partly formed an accumulation of cells in the G0/G1 and G2/M phases of the cell cycle in human hepatocellular carcinoma HepG2 cells	[21]
	Anticancer metastasis	Induced heme oxygenase-1(HO-1) expression and subsequently decreased ROS generation and VSMC activation induced by TNF-α	[37]
Hesperidin	Suppress proliferation	Promoted apoptosis via conducting the expression of p53 and PPAR γ and suppressing the activation of NF-κB in leukemia cell NALM-6	[27]
Flavonoids extracted from Korean Citrus aurantium L.	Cell cycle arrest	Induced non-small-cell lung cancer (NSCLC) A549 cells arrest at the G2/M checkpoint	[18]
	Suppress proliferation	Induced caspase-dependent apoptosis through AKT pathway by inhibiting expression of XIAP and Bcl-2 in human leukemia cells U937	[26]
Gold lotion	Suppress proliferation	In azoxymethane-induced aberrant crypt foci formation, it downregulated the protein levels of iNOS, COX-2, ornithine decarboxylase, VEGF, and matrix metallopeptidase 9 in colonic tissues of mice	[31]
	Anticancer metastasis	Downregulated MMP-2 and MMP-9 protein expression levels and reduced tumor volumes and weights in human prostate tumor xenograft mouse model	[39]
	Antiangiogenesis	Significantly suppressed the protein expression level of VEGF	[39]
		Reduced the protein levels of VEGF in AOM-induced colonic tissues	[31]