Milk Proteins, Peptides, and Oligosaccharides: Effects against the 21st Century Disorders

Table 2

Chemopreventive properties of lactoferrin and its derived peptide lactoferricin against cancer demonstrated by cell culture experiments and animals models.

Type of cancer	Animal species/protein-peptide	Cell line/animal model	Effects/mechanisms of action	Reference
Breast cancer	Human lactoferrin	MDA-MB-231 cells	Inhibition of cell growth; Cell cycle arrest	[160]
	Bovine lactoferrin	4T1 xenograft Balb/c mice	Improvement of tamoxifen chemopreventive effects; Downregulation of proinflammatory cytokines	[161]
	Bovine lactoferrin-oleic acid complex	MCF-7 cells	Inhibition of proliferation; Induction of apoptosis	[162]
	Bovine lactoferricin	MCF-7, T-47D, and MDA-MB-435 cells	Cytotoxic activity; Induction of apoptosis	[163]
Colon cancer	Camel lactoferrin	HCT-116 cells	Inhibition of cell proliferation; Antioxidant activity; Inhibition of DNA damage	[164]
	Bovine lactoferrin	Caco-2 xenograft mouse model	Inhibition of tumor growth	[165]
	Bovine lactoferrin-oleic acid complex	HT-29 cells	Inhibition of proliferation; Induction of apoptosis	[166]
		C26 cells	Cytotoxic activity	[118]
		Caco-2 cells	Inhibition of cell proliferation	[166]
			Cell cycle arrest by downregulation of cyclin E1
	Bovine lactoferricin	Ultraviolet-irradiated Caco-2 cells	Reduction of DNA damage; Cell cycle arrest by downregulation of cyclin E1	[167]
		Colo-35 and HT-29 cells	Cytotoxic activity/induction of apoptosis	[163]
Cervical cancer	Bovine lactoferrin	HeLa cells	Inhibition of cell growth; Induction of nuclear accumulation of Smad-2	[168]
Fibrosarcoma	Bovine lactoferricin	Meth A cells	Cytotoxic activity; Tumor cell membrane disruption	[118]
Head and neck cancer	Human lactoferrin	Squamous carcinoma O12 tumor bearing mice	Reduction of tumor; Immunomodulatory effects	[169]
Hepatocarcinoma	Bovine lactoferrin-oleic acid complex	HepG2 cells	Inhibition of proliferation; Induction of apoptosis	[162]
Leukemia	Bovine lactoferricin	THP-1 human monocytic leukemic cells	Induction of apoptosis; Activation of ROS generation and Ca^2+/Mg^2+-dependent endonucleases	[170]
		Jurkat T leukemia cells	Induction of apoptosis by triggering mitochondrial swelling and release of cytochrome c; Induction of cell membrane permeabilization	[163, 171]
			Activation of ROS generation and caspase-3 and caspase-9 activity; Reduction of DNA methyltransferases expression	[172]
Lymphoma		Raji and Ramos Burkitt's B-lymphoma cells	Induction of apoptosis; Stimulation of DNA fragmentation, chromatin condensation, and nuclear disintegration	[114]
		Ramos B-lymphoma cells xenografts in SCID/beige mice	Extension of survival of mice	[114]
	Bovine lactoferricin	A20 cell lymphomas in syngeneic Balb/c mice	Tumor necrosis and regression of the tumors; Induction of long-term specific cellular immunity	[173]
		B16-BL6 melanoma and L5178Y-ML25 lymphoma cells metastasis models in syngeneic mice	Inhibition of tumor metastasis in lung	[117]
Lung cancer	Bovine lactoferrin	A549 cells; Transgenic mice overexpressing hVEGF-A165	Downregulation of proinflammatory cytokines Suppression of tumor development	[174]
Melanoma	Bovine lactoferricin	B16F10 cells	Cytotoxic activity	[118]
		Spontaneous B16-BL6 metastasis models in syngeneic mice	Inhibition of tumor metastasis in lung	[117]
Nasopharyngeal; carcinoma	Human lactoferrin	5–8F, CNE2, and HONE1 cells; Xenograft Balb/c mice	Suppression of tumorigenesis through inhibition of the AKT pathway	[175]
Neuroblastoma	Bovine lactoferricin	Human MYCN-amplified and non-MYCN-amplified neuroblastoma cells	Cytotoxic activity; Destabilization of the cytoplasmic membrane; Activation of caspase-6, caspase-7, and caspase-9	[119]
		SH-SY-5Y neuroblastoma xenografts in nude rats	Reduction of the tumor growth	[119]
Oral cancer	Bovine lactoferricin	Oral squamous carcinoma SAS cell	Induction of apoptosis; Cleavage of caspase-3 and poly-ADP ribose polymerase; Phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase/stress activated protein kinase	[176]
Ovarian cancer	Bovine lactoferricin	Skov3 and Caov3	Cytotoxic activity; Induction of apoptosis	[163]