Table 1.

Anticancer activities of lactoferrin and lactoferricin.

Cancer Type	Mechanism of Anticancer Action	References
Breast	hLf causes arrest in the G0/G1 phase, induction of cell apoptosis and regulation of the expression of Bcl-2, Bax and activation of caspase 3.	[94]
Cervix	hLf inhibits cervical cancer due to elevated expression of Fas and decreased the ratio of anti- to pro-apoptotic molecule Bcl-2/Bax.	[95]
Colon	Lfcin causes arrest in the at S phase through downregulation of cyclin E1 in CaCO2 cells.	[96]
	hLF increases expression of TGF-β1, and holo-forms of LFs stimulate IL-18 secretion in CaCO2 cells.	[97]
	Lf induces caspase-1 and IL-18.	[98]
	bLf increases production of CD4+, CD8+, and IL-18	[99]
Gastric	BLfcin induces apoptosis human gastric cancer cell line AGS.	[100]
Head, neck, and oral	Lf induces suppression of AKT signaling via inhibition of 3-phosphoinositide-dependent protein kinase-1 expression and/or blocking of the K18-14-3-3 complex.	[101]
	bLf and [Polyphenon-B (P-B)] P-B was more effective in inhibiting hamster buccal pouch (HBP) carcinogenesis by inhibiting oxidative DNA damage, carcinogen activation, cell proliferation, invasion, and angiogenesis.	[102]
	Lf inhibits tumor through direct cellular inhibition and immunomodulation.	[103]
	Lf causes cell cycle arrest through downregulation of cyclin-dependent kinases and upregulation of p27 protein expression in head and neck cancer cell lines.	[104]
	Lf derivated peptides induce apoptosis via JNK/SAPK activation in squamous cell carcinoma cell line SAS.	[105]
Leukemia	LfcinB6 (RRWQWR) induces citoxicity via caspase-mediated and cathepsin B-mediated mechanism in T-leukemia cells.	[106]
	Lfcin kills T-leukemia cells by triggering the mitochondrial pathway of apoptosis and through the generation of reactive oxygen species.	[107]
	LF11-322 (PFWRIRIRR-NH2), peptide fragment derived from human lactoferricin, induces necrosis in leukemia cells (MEL and HL-60 leukemia cells).	[108]
	Lf increases CDK6 and hyper-phosphorylated retinoblastoma protein, resulting in the induction of E2F1-dependent apoptosis in Jurkat human leukemia T lymphocytes.	[109]
Lung	bLf inhibits NNK-induced mouse lung tumorigenesis, through the modification of cell proliferation and/or apoptosis.	[110]
	hLf inhibits the growth of head and neck squamous cell carcinoma via direct cellular inhibition as well as systemically via immunomodulation.	[103]
	Lf shows antiproliferative effects via hypophosphorylation of Rb on H1299 cells.	[111]
	Lfcin inhibits VEGF expression and induces apoptosis on non-small cell lung cancer H460.	[112]
NCS	Lfcin inhibits tumor growth and induces apoptosis through activation of caspases in neuroblastoma cells and in vivo).	[113]
	Lf causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line (downregulation of cyclin D1 and D4). Administration of hLf with TMZ enhanced the effect of chemotherapy both in vitro and in vivo.	[114]