“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

Sun, Xueying; Jiang, Ruohan; Przepiorski, Aneta; Reddy, Shiva; Palmano, Kate; Krissansen, Geoffrey W.

doi:10.1186/1471-2407-12-591

Cited by 41 publications

(29 citation statements)

References 55 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

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

2013

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Previous studies on postmortem human brain tissue have shown that the iron-binding glycoprotein lactoferrin is upregulated in dopamine (DA) neurons resistant to degeneration in Parkinson disease (PD). To study how this could possibly relate to disease progression, we used midbrain cultures and experimental settings that model the progressive loss of DA neurons in this disorder. Human lactoferrin of either recombinant or natural origin provided robust protection to vulnerable DA neurons in a culture paradigm in which these neurons die spontaneously and selectively as they mature. The efficacy of lactoferrin was comparable to that of glial cell line-derived neurotrophic factor, a prototypical neurotrophic factor for DA neurons. Neuroprotection by lactoferrin was attributable to its binding to heparan sulfate proteoglycans on the cell surface of DA neurons and subsequently to partial inactivation of focal adhesion kinase (FAK), a major effector kinase of integrins. We established that FAK inactivation served to unmask a prosurvival phosphoinositide 3-kinase/AKT-dependent signaling pathway that stimulates calcium shuttling from endoplasmic reticulum to mitochondria. DA neurons exposed to the mitochondrial toxin 1-methyl-4-phenylpyridinium were also partially protected by lactoferrin, further supporting the view that mitochondria may represent a downstream target for lactoferrin protective actions. Finally, we found that the iron binding capability of lactoferrin intervened in DA cell rescue only when neurodegeneration was consecutive to iron-catalyzed oxidative stress. Overall, our data suggest that the accumulation of lactoferrin in PD brains might be evidence of an attempt by the brain to minimize the consequences of neurodegeneration.

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Section: Resultsmentioning

confidence: 99%

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

2013

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“…Generally, hLf and bLf have been shown to exert anti-cancer activity for both tumor prevention and treatment [18,109]. The Lf preventive effect has been demonstrated in several animal models bearing different types of tumors, including lung, tongue, esophagus, liver, and colorectal [110][111][112][113], whereas Lf treatment was found efficient in inhibiting growth, metastasis, and tumor-associated angiogenesis [18,114,115], as well as in boosting chemotherapy [116,117].…”

Section: Lactoferrin and Cancermentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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“…In particular, lactoferrin, a whey protein, has been demonstrated, in vitro , to inhibit the growth of breast cancer (MDA‐MB‐231) and nasopharyngeal carcinoma cells by, respectively, arresting the cell cycle at the G1/S transition and suppressing Akt signalling (Damiens et al , ; Deng et al , ). Studies in mouse model in vivo confirmed its anticancer activity against head‐and‐neck squamous cell carcinoma (Varadhachary et al , ) and demonstrated an improvement in the chemotherapeutic effects of tamoxifen in 4 T1 breast cancer (Sun et al , ).…”

Section: Methodsmentioning

confidence: 94%

Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review

Cicero

Fogacci

Colletti

2016

British J Pharmacology

259

144

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“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

Cited by 41 publications

References 55 publications

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

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

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review

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