Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor

Abstract

Lung cancers are among the most common cancers in the world, and the search for effective and safe drugs for the chemoprevention and therapy of pulmonary cancer has become important. In this study, bovine lactoferrin (bLF) was used in both in vitro and in vivo approaches to investigate its activity against lung cancer. A human lung cancer cell line, A549, which expresses a high level of vascular endothelial growth factor (VEGF) under hypoxia, was used as an in vitro system for bLF treatment. A strain of transgenic mice carrying the human VEGF-A165 (hVEGF-A165) gene, which induces pulmonary tumors, was used as an in vivo lung cancer therapy model. We found that bLF significantly decreased proliferation of A549 cells by decreasing the expression of VEGF protein in a dose-dependent manner. Furthermore, oral administration of bLF at 300 mg/kg of body weight 3 times a week for 1.5 mo to the transgenic mice overexpressing hVEGF-A165 significantly eliminated expression of hVEGF-A165 and suppressed the formation of tumors. Additionally, treatment with bLF significantly decreased the levels of proinflammatory cytokines, such as tumor necrosis factor-α, and antiinflammatory cytokines, such as IL-4 and IL-10. Levels of IL-6, which is both a proinflammatory and an antiinflammatory cytokine, were also reduced. Treatment with bLF decreased levels of tumor necrosis factor-α, IL-4, IL-6, and IL-10 cytokines, resulting in limited inflammation, which then restricted growth of the lung cancer. Our results revealed that bLF is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer.

The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis

“…Astrocytes that divide from immature precursor cells may intervene actively in DA cell demise in this culture paradigm (Mourlevat et al, 2003), suggesting that the protective effect of lactoferrin against the spontaneous loss of DA neurons may possibly result from an indirect effect on dividing glial cells. Also in support of this possibility, lactoferrin was reported to inhibit the growth of some cancer cells (Zemann et al, 2010;Tung et al, 2013) and to improve the therapeutic effects of anticancer therapies (Sun et al, 2012). Hence, we wished to determine whether the proliferation rate of astrocytes or their precursor cells (both cell populations represent more than 95% of dividing cells at this stage of the cultures) was affected by Lf in midbrain cultures.…”

In vitro and in vivo effect of human lactoferrin on glioblastoma growth

“…To discover new substances that can improve the standard GBM treatment, we have focused our attention on human lactoferrin (HLF), a natural agent with no toxicity 16 that has been shown to inhibit both the development of experimental metastases 4 in mice and the growth of intestinal, head, and neck cancer in an in vitro human cancer cell model. 8,30 This negative effect of HLF on cell proliferation may be ascribed to the altered expression or activity of regulatory proteins. Lactoferrin-dependent, cytokine-mediated stimulation of the activity of natural killer (NK) cells and CD4+ and CD8+ lymphocytes represents an important factor in the defense against tumor growth.…”

Clinical applications of bioactive milk components

“…40 The inhibition of tumor growth in animal studies has been attributed to the anti-angiogenic and anti-inflammatory functions of lactoferrin. 41 Clearly, further study is warranted to explore the application of lactoferrin in the treatment of lung cancer and other malignancies.…”