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

Abstract

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.

Peptides Derived from (RRWQWRMKKLG)2-K-Ahx Induce Selective Cellular Death in Breast Cancer Cell Lines through Apoptotic Pathway

“…Our results are exceptionally relevant because these dimeric peptides exhibited a selective cytotoxic effect against breast cancer cell lines better than BLF, which also exhibited inhibitory effects on the growth of four breast cancer cell lines, T-47D, MDA-MB-231, Hs578T, and MCF-7, but not for the normal breast cell line MCF-10-2A [34,39,41,45]. LfcinB showed considerable potential as an anti-cancer agent because the peptide is able to trigger apoptosis in a wide range of breast cell lines (MDA-MB-435, MDA-MB-231, T-47D, and MCF-7) without damaging normal human cells such as lymphocytes, erythrocytes, endothelial cells, fibroblasts, and breast epithelial cells [37,40,46].…”

“…LFB and LfcinB are candidates for alternative cancer treatment with the same advantages but without the side effects that characterize standard therapies [45]. A major limitation of the therapeutic efficacy for cancer is usually the systemic bio-distribution, which often leads to reduced bioavailability of the drug delivered to the cancer cells, and consequently to a reduction in the therapeutic index [45].…”

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

“…Following infection or inflammatory stimuli, IL-6 up-regulation, both through hepcidin- dependent 41 or independent pathways, 42 , 43 leads to Fpn downregulation, thus activating an unsafe intracellular iron overload which increases host susceptibility to infection 23 or cancer proliferation. 21 , 44 It is important to underline that the Fpn localization is also pivotal. As a matter of fact, in bronchial epithelium, Fpn, located on the cell apical side, acts as an iron detoxifying agent, able to translocate the metal in the bronchial lumen, thus allowing its further removal by the ciliary pathway.…”

“…Several efforts have been made to decipher the molecular mechanisms and the concurrent factors involved in cancer development and proliferation and, among these, iron represents an important risk factor. 21 .…”

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

“…Lactoferrin exhibits a broad-spectrum antimicrobial activity against bacterial, viral, and fungal infections. It also appears to exhibit a clinically relevant activity against some forms of cancer [ 295 ], cystic fibrosis [ 296 ], and necrotizing enterocolitis [ 297 ]. Literature indicates that lactoferrin exhibits activity against a wide range of RNA and DNA viruses, including cytomegalovirus, herpes simplex viruses, HIV, HCV, poliovirus, hantaviruses, rotaviruses, human respiratory syncytial virus, and others [ 298 , 299 ].…”