[#2005-04] Are Botanical Glucans Effective in Enhancing Tumoricidal Cell Activity?, S. Rundles-Cunningham et al.

Are Botanical Glucans Effective in Enhancing Tumoricidal Cell Activity?

Cunningham-Rundles S, Lin H, Cassileth B

Department of Pediatrics, The Weill Medical College of Cornell University, New York, NY

Studies of nutrient immune interactions have shown that protein calorie malnutrition and micronutrient deficiency impair immune development and immune response especially in critical phases of life. More recently, important data on the role of fatty acids in immune responses has emerged. The question of how or when dietary intervention might augment immune response or reduce any specific disease expression remains open. A fundamental issue is how to design an experimental approach that reveals key relationships so that we can examine relevant change. Current studies on how the adaptive immune response is regulated by the innate immune response in the microenvironment may be particularly useful, because this may be the level at which nutrient action occurs. One common pathway for the action of certain carbohydrates isolated from mushroom, barley, and other sources, including various microbes, may involve effects on cellular differentiation and trafficking from bone marrow and other hematopoietic sites. We have been working with a purified extract from the Maitake mushroom (Grifola frondosa) with the objective of studying the effects of MD-fraction as an oral adjuvant in cancer patients. Previous studies in the mouse have used intraperitoneal or intravenous injection to assess the effects of Maitake mushroom on the growth of implanted tumors and various adjuvant-like effects have been observed. However, dose-response relationships were elusive. Because some other beta-glucans appear to promote mobilization of hematopoietic stem cells, we used a colony-forming assay (CFU-GM) to study the effects of MD-fraction (MDF) on hematopoietic stem cells. We found a dose-response effect on mouse bone marrow cell (BMC) hematopoiesis in vitro. The data showed that the addition of MDF significantly enhanced the development of CFU-GM. The mechanism of action included significant increase of nonadherent BMC viability even in the presence of doxorubicin (DOX). MDF promoted BMC viability and protected CFU-GM from DOX-induced toxicity. In addition, MDF treatment promoted the recovery of CFU-GM colony formation after BMCs were pretreated with DOX. We have extended these observations to human cord, and peripheral blood and to cell lines and observed that this botanical activates a selective pattern of response that may model the effects of other dietary elements on immune response.