A
NTICANCER
R
ESEARCH
34
: 3569-3578 (2014)
MARCO RUGGIERO
1,4
, EMMA WARD
2
, RODNEY SMITH
2
, JACOPO J.V. BRANCA
3
, DAVID NOAKES
4
,GABRIELE MORUCCI
3
, MARGIT TAUBMANN
5
, LYNDA THYER
2
and STEFANIA PACINI
3
1
Department of Experimental and Clinical Biomedical Sciences, University of Firenze, Firenze, Italy;
2
Macro Innovations Ltd, Cambridge, UK;
3
Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy;
4
Immuno Biotech Ltd, Guernsey, Channel Islands, UK;
5
Naturheilzentrum, Bayreuth, Germany
0250-7005/2014 $2.00+.40
Abstract.
Background: Oleic Acid (OA) has been shown tohave anticancer properties mediated by interaction with proteins such as
α
-lactalbumin and lactoferrins. Therefore, wesynthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per secancer cell proliferation and metastatic potential. Wehypothesised that OA-GcMAF complexes could exploit theanticancer properties of both OA and GcMAF in a synergisticmanner. 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 weretreated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination witha low-carbohydrate, high-protein diet, fermented milk productscontaining naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid. Results: Measuring the tumour by ultrasonographic techniques, weobserved 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 immunesystem stimulation and tumour volume reduction avoidingharmful side-effects.
It is well-assessed that Oleic Acid (OA), a recognisedfundamental component of healthy diets (1), showsanticancer properties (2) that contribute to the increase inlongevity and reduced risk of mortality and morbidityassociated with its consumption (1). Although the precisemolecular mechanism responsible for its anticancerproperties is not completely understood (2), it appears thatOA is involved in intracellular calcium signalling associatedwith the induction of cancer cell apoptosis. It has been proposed that the anticancer effects of OA aremediated by its interaction with proteins highly representedin biological fluids such as
α
-lactalbumin and lactoferrins.These proteins bind OA to form OA-protein complexeswhich exhibit highly selective anti-tumour activity
in vitro
and
in vivo
(3). Soon after their identification, thesecomplexes were labelled as HAMLET an acronym thatstands for “human
α
-lactalbumin made lethal to tumourcells”, even though further studies demonstrated that
α
–lactalbumin is not the sole protein forming such complexes.Thus, other proteins, forming complexes with OA, exhibitidentical anticancer properties (4). It is now accepted thatthese OA-protein complexes destroy tumour cells with highselectivity and with no evidence of toxicity for normaltissues, a key feature in the quest for anticancer treatmentsdevoid of toxic side effects.Study of the structural characteristics of such anticancerOA-protein complexes demonstrated that a commonmolecular feature is the tendency toward OA-induced proteinoligomerization. Since OA-induced oligomerization has beenreported for a number of proteins in addition to thoseinitially identified in HAMLET, it was hypothesised that thisphenomenon may be inherent to many proteins (5). Some of the proteins forming OA-protein anticancercomplexes such as
α
-lactalbumin and lactoferrins are highlyrepresented in milk. These compounds are known to exertpowerful stimulatory effects on the immune system (6).These findings provide additional acceptance to thehypothesis that the immune system is directly involved in theoverall anticancer effects of OA-protein complexes.
3569
Correspondence to:
Jacopo J.V. Branca, Department of Experimental and Clinical Medicine, University of Firenze, LargoBrambilla 3, 50134 Firenze, Italy. Tel: +39 0552758067, Fax: +390554379500, e-mail: jacopo.branca@libero.it
Key Words:
Oleic acid, nitric oxide, macrophages, human cancer,vitamin D, Gc protein-derived macrophage activating factor.
A
NTICANCER
R
ESEARCH
34
: 3569-3578 (2014)
Oleic Acid, Deglycosylated Vitamin D-Binding Protein, Nitric Oxide: A Molecular Triad Made Lethal to Cancer
MARCO RUGGIERO
1,4
, EMMA WARD
2
, RODNEY SMITH
2
, JACOPO J.V. BRANCA
3
, DAVID NOAKES
4
,GABRIELE MORUCCI
3
, MARGIT TAUBMANN
5
, LYNDA THYER
2
and STEFANIA PACINI
3
1
Department of Experimental and Clinical Biomedical Sciences, University of Firenze, Firenze, Italy;
2
Macro Innovations Ltd, Cambridge, UK;
3
Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy;
4
Immuno Biotech Ltd, Guernsey, Channel Islands, UK;
5
Naturheilzentrum, Bayreuth, Germany
0250-7005/2014 $2.00+.40
https://www.scribd.com/document/318929358/Anticancer-Research-Clinic
