Lentinan: Hematopoietic, Immunological, and Efficacy Studies in a Syngeneic Model of Acute Myeloid Leukemia

Abstract

Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

Cross-Species Functional Genomic Analysis Identifies Resistance Genes of the Histone Deacetylase Inhibitor Valproic Acid

“…To further explore the VPA-resistance mechanisms we utilized the Brown Norwegian myeloid leukemia (BNML) syngeneic rat leukemia model which provides highly reproducible responses to conventional chemotherapeutics [18], [36] with the advantage of a complete host immune system during leukemia growth and therapy. We developed a progressive disease model in the BNML rats by giving animals suboptimal doses of VPA (170 mg/kg b.i.d.…”

Immune modulating effects of β-glucan

“…Preclinical data show good evidence for a beneficial effect of b-glucan in cancer [38][39][40]; however, there is some debate about whether these effects are due to direct cytotoxic effects or immunomodulatory mechanisms [41,42]. For example, Yoon et al reported that b-glucan purified from mutated S. cerevisiae inhibited lung metastasis of colon 26-M3.1 carcinoma that was associated with splenocyte proliferation, tumoricidal activity of peritoneal macrophages, and NK cell cytotoxicity but there was no effect of this treatment on direct cytotoxicty of colon 26-M3.1 cells in vitro [43].…”

Stimulation of human monocytic cells by the medicinal mushroom Agaricus blazei Murill induces expression of cell surface markers associated with activation and antigen presentation

“…In particular, the potential role of medicinal mushrooms as adjuvant therapy for solid tumors and acute leukemia has been extensively investigated [12][13][14][15]. The edible Bacidiomycota mushroom Agaricus blazei Murill (AbM) grows naturally in an area near São Paulo, Brazil, where it has been used in traditional medicine against a variety of diseases, including infection and cancer [16].…”