Lactoferrin is a glycoprotein from the transferrin family that has the ability to bind to iron. It is found in body secretions such as milk, tears, saliva, nasal secretions and in polymorphonuclear cells, neutrophils. Human colostrum ( breast milk ) is the natural source with the highest concentration of lactoferrin. Human milk as well as cow’s milk are rich in this protein.
Lactoferrin plays a key role in iron metabolism. These include the transport of iron, the delivery of iron to the cells and the control of iron in the body’s secretions. Cell proliferation, antimicrobial activity and anticancer activity are some of the other very important functions of lactoferrin. The antimicrobial action of transferrin has been well explained in the literature. Microorganisms are highly dependent on iron as a substrate, which is essential in DNA synthesis during their cell cycle. One of the main abilities of lactoferrin is to hide free iron. For that reason, microorganisms cannot satisfy their needs for free iron. By suppressing the division of microorganisms, it allows other cells of the human immune system to attack the remaining cells and destroy them. Lactoferrin is the initiator of the action of the immune system and its immune effect is transmitted through secretions in the body, which I have already mentioned. Lactoferrin can bind to iron even in an environment with very low pH values. This is very important because in hot spots of inflammation, the pH value can fall below 4.5. Similar mechanisms have been suggested as an anticancer ability of lactoferrin. Cancer cells have a very pronounced division. The need for iron to maintain the cell cycle is greater even than the above-mentioned division of microorganisms. Thus, by depriving iron, lactoferrin very successfully inhibits tumor growth. New discoveries suggest that other complex biological pathways are also involved in the protective mechanisms of lactoferrin against cancerous diseases, separate from its basic mechanisms listed above. These special multifunctional processes of lactoferrin are related to its action on specific receptors located on the surface of target cells.
The anticancer activity of lactoferrin was evaluated on tumor cells both in vitro and in vivo. Suppression of the cell cycle (preventively inhibited DNA synthesis) is a hypothesis that, as the main mechanism, initiated the research of the chemotherapeutic effects of lactoferrin.
In one study, Dr. Xueying Sun and other team members, lactoferrin was combined with tamoxifen in the treatment of breast cancer. Tamoxifen is an anti-cancer drug that is mainly effective for the estrogen receptor positive type of breast cancer. But it also has a very small effect on the estogen receptor negative type of breast cancer. In this study, they tried to find out whether lactoferrin can increase the effect of tamoxifen on the estrogen-negative type of breast cancer. Iron-saturated lactoferrin from cow’s milk was used for oral feeding of female mice. Two models were set up in the study: a preventive model and a treated model. In the preventive model, oral lectofein diet and tamoxifen injections were started 2 weeks later, 4T1 carcinogenic cells were injected into the milk tissue. Tumor growth, metastasis, body weight, and interleukin 18 levels (also called interferon Y inhibitory factor that has the ability to activate cells that have anti-cancer abilities) were analyzed. The results were as follows. Tamoxifen given weekly inhibited 4T1 proliferation in vitro. In a tumor prevention model, a diet with lectoferrin in combination with tamoxifen caused a 4-day delay in tumor formation and significantly inhibited tumor growth and liver and lung metastases compared with untreated groups. Combination therapy was significantly more effective than monotherapy. Lactoferrin reduced the weight loss caused by tamoxifen and the effect of cancer. It also prevented the reduction of interleukin 18 and interferon in the blood. It also enhanced cellular mediators and initiated the activation of the immune mechanism and cells that have anti-cancer abilities at the sites where the cancer was located. Similar positive effects have been seen on the vitality of tumor cells. The researchers concluded: “The results indicate that iron-saturated lactoferrin is a potent natural supplement that can increase the chemotherapeutic activity of tamoxifen. This preparation could play a decisive role in patients who have ER-negative breast cancer and are being treated with tamoxifen. “
A similar study was done by Dr. DC Duarte and others involved in evaluating the effect of cow’s milk lactoferrin on human breast cancer cell lines, HS578T and T47D. Unlike the above study, tamoxifen was not used as an antitumor agent. One portion of the cancer cells were treated with increased concentrations of lactoferrin until the control group was given this compound. According to the results of the researchers, lactoferrin reduced the vitality of cancer cells in both cell lines by about 50%. It also increased apoptosis (cancer cell death) by about two times for both cell lines. The profiling rate has also been significantly reduced. Cell migration showed a significant decrease in the T47D cell line, in the presence of lactoferrin. This study clearly shows that lactoferrin prevents most of the processes of cancer progression and metastasis. However, this study did not concentrate on the anti-cancer effects of lactoferrin.
A study conducted by S. Penco et al included the effect of lactoferrin on the expression of human breast cancer. Of the 78 samples, 31 were negative for mRNA expression. Further analysis showed a negative correlation between estrogen receptor expression and lactoferrin expression. This suggests that lactoferrin expression in breast cancer is mediated through many complex mechanisms of action. Although this study did not enter into the therapeutic effects of lactoferrin, the information obtained is very important for planning further research on the treatment of breast cancer.
The second study was conducted by Dr. Xu and others. They investigated the effect of bovine lactofein on gastric cancer. Their main focus was on cancer cell apoptosis and its effect on the AKT signaling pathway. The ACT pathway promotes cell survival in response to extracellular signals. Inhibition of this provides an active way to treat cancer. In this study, gastric cancer cells were exposed to lactofein for 24 and 48 hours. Cell vitality and apoptosis were quantitatively assessed. According to the results, inhibition of cancer cells was seen in both treatment time periods. The ATK signaling pathway was included in this study to elucidate the mechanisms of action of lactofein as an anti-tumor agent. The researchers identified inhibition of ATK passage and the regulatory effects of reducing the effects of proteins that resulted in apoptosis of human gastric cancer cells, which was a great success.
Dr. Xiao and others launched a study to discover the effects of lactofein on head and neck cancer. The main goal of the research was to identify the molecular mechanisms of lactoferrin in induced inhibition of cancer cell growth. Growth arrest was seen in three of the four cases of cell lines tested in this study. Inhibition of G0-G1 in part of the cell cycle was seen as a mechanism involved in this process.
Dr. N. Sakamoto did research on the effects of lactofein on pancreatic cancer both in vitro and in vivo. Inhibitory effects were found in cancer lines in both cases.
Similar studies have been done on other known cancer cell lines such as cancer prostate , cervical and oral cancer with the use of lactoferrin. All studies have yielded very promising results. Further studies should be performed in combination with other chemotherapeutic agents to find the most effective combination for cancer treatment.