The Science of Bravo – Oleic Acid, Deglycosylated Vitamin D-Binding Protein, Nitric Oxide: A Molecular Triad Made Lethal to Cancer

Abstract. Background: Oleic Acid (OA) has been shown to have anticancer properties mediated by interaction with proteins such as α-lactalbumin and lactoferrins. Therefore, we synthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per se cancer cell proliferation and metastatic potential. We hypothesised that OA-GcMAF complexes could exploit the anticancer properties of both OA and GcMAF in a synergistic manner. We postulated that the stimulating effects of GcMAF on macrophages might lead to release of nitric oxide (NO). Patients and Methods: Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA- GcMAF-based integrative immunotherapy in combination with a low-carbohydrate, high-protein diet, fermented milk products containing naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid. Results: Measuring the tumour by ultrasonographic techniques, we observed a decrease of tumour volume of about 25%. Conclusion: These observations demonstrate that OA, GcMAF and NO can be properly combined and specifically delivered to advanced cancer patients with significant effects on immune system stimulation and tumour volume reduction avoiding harmful side-effects.

It is well-assessed that Oleic Acid (OA), a recognised fundamental component of healthy diets (1), shows anticancer properties (2) that contribute to the increase in

longevity and reduced risk of mortality and morbidity associated with its consumption (1). Although the precise molecular mechanism responsible for its anticancer properties is not completely understood (2), it appears that OA is involved in intracellular calcium signalling associated with the induction of cancer cell apoptosis.

It has been proposed that the anticancer effects of OA are mediated by its interaction with proteins highly represented in biological fluids such as α-lactalbumin and lactoferrins. These proteins bind OA to form OA-protein complexes which exhibit highly selective anti-tumour activity in vitro and in vivo (3). Soon after their identification, these complexes were labelled as HAMLET an acronym that stands for “human α-lactalbumin made lethal to tumour cells”, even though further studies demonstrated that α- lactalbumin is not the sole protein forming such complexes. Thus, other proteins, forming complexes with OA, exhibit identical anticancer properties (4). It is now accepted that these OA-protein complexes destroy tumour cells with high selectivity and with no evidence of toxicity for normal tissues, a key feature in the quest for anticancer treatments devoid of toxic side effects.

Study of the structural characteristics of such anticancer OA-protein complexes demonstrated that a common molecular feature is the tendency toward OA-induced protein oligomerization. Since OA-induced oligomerization has been reported for a number of proteins in addition to those initially identified in HAMLET, it was hypothesised that this phenomenon may be inherent to many proteins (5).

Some of the proteins forming OA-protein anticancer complexes such as α-lactalbumin and lactoferrins are highly represented in milk. These compounds are known to exert powerful stimulatory effects on the immune system (6). These findings provide additional acceptance to the hypothesis that the immune system is directly involved in the overall anticancer effects of OA-protein complexes.

The Article is here: Anticancer Res lavoro