PMID: 

Int J Cancer. 2004 Sep 1 ;111(3):398-403. PMID: 15221967

Abstract Title: 

Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy.

Abstract: 

In this work, we investigated the anticancer activity of orally administered recombinant human lactoferrin (rhLF) alone and in combination with chemotherapy in tumor-bearing mice. rhLF inhibited the growth of squamous cell carcinoma (O12) tumors in T cell-immunocompromised nu/nu mice by 80% when administered at 1,000 mg/kg (2.9 g/m2) by oral gavage twice daily for 8 days (p

read more

PMID: 

Cancer Res. 1994 May 1 ;54(9):2310-2. PMID: 8162571

Abstract Title: 

Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice.

Abstract: 

The antitumor effects of the multifunctional iron-binding glycoprotein, lactoferrin (Lf), were investigated. Lf inhibited growth in mice of transplantable solid tumors induced by v-ras transformed fibroblasts and a methylcholanthrene-induced fibrosarcoma. Lf also substantially reduced lung colonization (experimental metastasis) by B16-F10 melanoma cells in syngeneic mice. Iron-saturated and apo-Lf exhibited comparable levels of tumor inhibition and antimetastatic activity. Transferrin, a related iron-binding protein, had no effect on lung colonization. In the B16-F10 system, elimination of natural killer cell activity by pretreatment of mice with anti-asialo GM1 antibody abrogated the effects of Lf, whereas inhibition of macrophage function with silica did not. The results demonstrate a novel activity for Lf and suggest a potentially important role for this molecule in the primary defense against tumorigenesis.

read more

PMID: 

Jpn J Cancer Res. 1999 Apr ;90(4):367-71. PMID: 10363572

Abstract Title: 

Lactoferrin inhibits hepatitis C virus viremia in patients with chronic hepatitis C: a pilot study.

Abstract: 

Hepatitis C virus (HCV) is associated with the development of cirrhosis and hepatocellular carcinoma. We recently found that bovine lactoferrin, a milk protein belonging to the iron transporter family, effectively prevented HCV infection in cultured human hepatocytes (PH5CH8). We tested the hypothesis that lactoferrin inhibits HCV viremia in patients with chronic hepatitis C. Eleven patients with chronic hepatitis C received an 8-week course of bovine lactoferrin (1.8 or 3.6 g/day). At the end of lactoferrin treatment, a decrease in serum alanine transaminase and HCV RNA concentrations was apparent in 3 (75%) of 4 patients with low pretreatment serum concentrations of HCV RNA. However, 7 patients with high pretreatment concentrations showed no significant changes in these indices. This pilot study suggests that lactoferrin is one potential candidate as an anti-HCV reagent that may be effective for the treatment of patients with chronic hepatitis.

read more

PMID: 

J Infect Dis. 2002 Oct 15 ;186(8):1161-4. Epub 2002 Sep 16. PMID: 12355368

Abstract Title: 

Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro.

Abstract: 

Enterovirus 71 (EV71), the newest member of Enterovirudae, is notable for its etiological role in epidemics of severe neurological diseases in children. It appears to be emerging as an important virulent neurotropic enterovirus in the upcoming era of poliomyelitis eradication, whereas no effective vaccine or antiviral agents are available at this moment. Human and bovine lactoferrins, iron-binding proteins belonging to the nonimmune defense system, were assayed in vitro to assess their inhibiting capacity on the cytopathic effect of EV71 on human embryonal rhabdomyosarcoma (RD) cells. Both bovine and human lactoferrins were found to be potent inhibitors of EV71 infection (mean IC(50), 10.5-24.5 microg/mL and 103.3-185.0 microg/mL, respectively). Lactoferrin probably exerts its effect at the level of viral adsorption, since the ongoing infection could not be further inhibited after the EV71 penetrated RD cells.

read more

PMID: 

Biochem Biophys Res Commun. 1998 Apr 17 ;245(2):549-53. PMID: 9571193

Abstract Title: 

Lactoferrin markedly inhibits hepatitis C virus infection in cultured human hepatocytes.

Abstract: 

We found that bovine lactoferrin (bLF), a milk protein belonging to the iron transporter family, effectively prevented hepatitis C virus (HCV) infection in cultured human hepatocytes (PH5CH8), a cell line susceptible to HCV infection and supportive of HCV replication. Because preincubation of HCV with bLF was required to prevent the infection of HCV to the cells, and preincubation of bLF with the cells showed no inhibitory effect on HCV infection, we demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF with HCV, but not due to the interaction of bLF with the cells. We further found that human lactoferrin also had anti-HCV activity, but bovine transferrin, the other member of the iron transporter family, did not have anti-HCV activity. Our findings suggest that lactoferrin is one of candidates for an anti-HCV reagent that will be well-tolerated and effective in the treatment of patients with chronic hepatitis.

read more

PMID: 

Nutr Cancer. 2014 ;66(8):1371-85. Epub 2014 Oct 30. PMID: 25356800

Abstract Title: 

Bovine lactoferrin induces cell cycle arrest and inhibits mTOR signaling in breast cancer cells.

Abstract: 

Lactoferrin (LF) is predominantly found in mammalian secretions with recognized anticancer potential, although the mechanisms involved in such activity are still unclear. Here, the stability, internalization, and cytotoxicity of bovine LF (bLF) and its variants were tested against a panel of breast cancer cells. bLF was found to be very stable under incubation with cells and also able to internalize them, although most of the protein remained in the culture medium. Furthermore, bLF (up to 30μM) inhibited the growth of breast cancer cells (T-47D, MDA-MB-231, Hs578T, and MCF-7) in a higher extent than in the normal counterpart cell line (MCF-10-2A), thus suggesting its selectivity. Regarding its variants, only the iron-saturated protein showed a higher activity compared with the commercial bLF. bLF growth inhibitory activity was associated with the induction of cell cycle arrest, but not with apoptosis. Moreover, exposure to bLF increased the cells phospho-AMPKα levels and decreased both phospho threonine mammalian target of rapamycin (mTOR) and total mTOR levels, indicating a novel mechanism of action through its ability to induce nutrient/energy-related stress. This study disclosed important findings to better understand the mechanisms underlying the bLF effects on breast cancer cell lines, which could be valuable for novel advances in the cancer research field.

read more

PMID: 

Early Hum Dev. 2014 Mar ;90 Suppl 1:S60-5. PMID: 24709463

Abstract Title: 

Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial.

Abstract: 

IMPORTANCE: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW,

read more

PMID: 

Carcinogenesis. 2004 Oct ;25(10):1961-6. Epub 2004 Jun 10. PMID: 15192017

Abstract Title: 

Lactoferrin enhances Fas expression and apoptosis in the colon mucosa of azoxymethane-treated rats.

Abstract: 

Bovine lactoferrin, a multifunctional glycoprotein, has been shown to strongly inhibit development of azoxymethane (AOM)-induced rat colon tumors. Little, however, is known about the inhibitory mechanisms. We have demonstrated recently that lactoferrin enhances the expression of a member of the tumor necrosis factor receptor family, Fas, in the colon mucosa during both early and late stages of carcinogenesis. Thus, Fas could be involved in bovine lactoferrin-mediated inhibition of tumor development. To investigate this possibility, we studied the influence of bovine lactoferrin on Fas-mediated apoptosis with regard to expression of Fas, activation of caspase-8 and caspase-3, and DNA fragmentation in the colon mucosa of AOM-treated rats. Western blot analysis demonstrated a>2.5-fold increase in Fas protein expression, as well as elevation of the active forms of both caspase-8 and caspase-3. Immunohistochemical analysis revealed Fas-positive cells and apoptotic cells preferentially within the proximal colon region, clearly at the site of bovine lactoferrin-mediated tumor inhibition. These results suggest that apoptosis caused by elevated expression of Fas is involved in chemoprevention by lactoferrin of colon carcinogenesis.

read more

PMID: 

J Nutr. 2010 Sep ;140(9):1552-6. Epub 2010 Jul 7. PMID: 20610637

Abstract Title: 

miR-214 regulates lactoferrin expression and pro-apoptotic function in mammary epithelial cells.

Abstract: 

Lactoferrin (Lf) is an abundantly expressed protein in human milk. Lactoferrin exhibits several important biological functions, and its expression is regulated by multiple environmental factors. Cellular endogenous factors, however, have not been extensively studied with regard to lactoferrin gene expression. In this study, we showed that lactoferrin gene expression and function are directly targeted by miR-214 in HC11 and MCF7 cells. In the lactoferrin mRNA 3 prime untranslated region (UTR) of human, mouse, rat, pig, bovine, camel, and goat species, there is a conserved region that perfectly matches the seed region of miR-214. Transfection of miR-214 mimic in HEK293 cells dose-dependently inhibited the activity of pGL3-control vector containing lactoferrin mRNA 3 prime UTR downstream of the luciferase gene. In HC11 cells, miR-214 overexpression inhibited the induction of lactoferrin expression by beta -estradiol (E2) and dexamethasone-prolactin-insulin (DPI). Furthermore, in MCF7 cells, overexpression of miR-214 markedly decreased lactoferrin expression (P lt 0.05), and inhibition of endogenous miR-214 expression increased lactoferrin expression and cellular apoptotic activities (P lt 0.05). In summary, our data showed that miR-214 is directly involved in lactoferrin expression and lactoferrin mediated cancer susceptibility (proapoptotic activities) in mammary epithelial cells.

read more

PMID: 

ORL J Otorhinolaryngol Relat Spec. 2003 Sep-Oct;65(5):245-9. PMID: 14730178

Abstract Title: 

Lactoferrin inhibits growth of malignant tumors of the head and neck.

Abstract: 

Lactoferrin, a naturally occurring glycoprotein found in breast milk, has previously been shown to have antimicrobial properties and recently has been demonstrated to inhibit malignant tumor growth, presumably through immunomodulation. We hypothesized that intratumoral injection of human and murine recombinant lactoferrin would decrease the growth of malignant tumors in vivo. Using an orthotopic murine model for both squamous cell carcinoma and fibrosarcoma of the floor of the mouth, we administered lactoferrin directly into the tumors using variable dosing strategies. Additionally, we performed in vitro experiments to assess whether the effects of lactoferrin are due to direct cytotoxicity. Our results revealed growth inhibition of 50% (p=0.03)and 54% (p=0.01) as compared with controls for both human and murine tumor cells in immunodeficient and immunocompetent mice, respectively. There was a more dramatic effect in immunocompetent models which may identify immunomodulation as an important mechanism of action for lactoferrin. Support for immunomodulation as a possible mechanism was the lack of any difference between controls and the experimental groups in vitro. Lactoferrin proved effective in reducing malignant tumor growth in a murine model. These properties offer hope for its use as a primary or adjuvant chemotherapeutic agent. Further investigation focused on mechanism and delivery is needed.

read more