Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

Abstract

Abstract. This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model.

Therapeutic Effects of Highly Purified De-Glycosylated Gcmaf in the Immunotherapy of Patients With Chronic Diseases

“…The beneficial effects observed in the immunotherapy of human tumours (Yamamoto et al, 2008a;2008b;2008c;Inui et al, 2013), have been confirmed in controlled experiments performed in several laboratories, where GcMAF proved effective against tumours transplanted into animals (Toyohara et al, 2011;Nonaka et al, 2012;Hirota et al, 2013) as well as in human cancer cells cultured in vitro (Gregory et al, 2010;Pacini et al, 2012a). In addition to the effects on tumour cells, we and others demonstrated that GcMAF inhibits cancer cell-induced angiogenesis, thus depriving the tumour cell mass of the blood, oxygen and nutrient supply that it needs to grow and metastasize (Kalkunte et al, 2005;Pacini et al, 2011;2012a;2012b).…”

A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages

“…There is indirect evidence suggesting that GcMAF activates macrophages that infiltrate experimental tumors in animal models [7,8]. This evidence, however, is indirect and, most important, refers to experimental tumors other than human breast cancer.…”

A thorny pathway of macrophage activating factor (GcMAF): from bench to bedside

“…При этом регистрируется снижение экспрессии опухолевыми клетками виментина, маркера прогрессии и метастазирования рака молочной железы, вызванного трансформацией эпителиальных клеток и приобретением ими фенотипа мезенхимальных клеток с повышенной устойчивостью к апоптозу, высокой миграционной актив ностью и инвазивностью (феномен эпителиальноме зенхимального транзита) (Pacini et al, 2012b;Thyer et al, 2013b). В экспериментах с золотистыми сирийскими хомяками в модели канцерогенеза, индуцированного 9,10-диметил-1,2-бензантраценом (DMBA), также был выявлен ингибирующий эффект GcMAF на рост опухоли и увеличение продолжительности жизни животных (Toyohara et al, 2011).…”