Bioactive Immunomodulatory Compounds: A Novel Combinatorial Strategy for Integrated Medicine in Oncology? BAIC Exposure in Cancer Cells

Abstract

The Standardized Cultured Extract of Lentinula edodes Mycelia (also known as Active Hexose Correlated Compound, AHCC) and Wasabia japonica (Wasabi) are natural nutritional supplements known for their immunomodulatory and anticancer potential. The aim of this study was to evaluate the combinatorial effect of the bioactive immunomodulatory compound (BAIC), obtained by combining Wasabi and AHCC, on human breast (MCF-7) and pancreatic (Panc02) adenocarcinoma cell lines. Data obtained revealed that BAIC determines a striking decline in cancer cell growth at minimal concentrations compared with the use of Wasabi and AHCC as single agents. A significant increase in the G0/G1 subpopulation together with a marked augmentation in the percentage of apoptotic cells was demonstrated by flow cytometry, together with a significant upregulation in the expression of genes associated to the apoptotic cascade in both cell lines. The inhibitory role BAIC plays in mammospheres formation from MCF-7-derived cancer stem cells was shown with a marked reduction in size and number. Interestingly, when BAIC was exposed to monocytic cells, no cytotoxic effects were observed. A monocytes-to-macrophages differentiation was rather observed with the concomitant acquisition of an anti-inflammatory phenotype. Taken together, our findings suggest that BAIC could be used as a potential integration of standard chemotherapy treatments because of the improved inhibitory activity on cancer cell proliferation and reduced potential adverse effects.

Combining the Anticancer and Immunomodulatory Effects of Astragalus and Shiitake as an Integrated Therapeutic Approach

“…Investigation of the anticancer activity of the mycelial extracts of Shiitake in combination with specific nutrients or other medicinal mushrooms has revealed positive findings. For example, a combination of the standardized cultured extract of Shiitake mycelia (also known as Active Hexose Correlated Compound, AHCC) and Wasabia japonica (Wasabi) (combinedly called Bioactive Immunomodulatory compound, BAIC) was tested for its effects on breast and pancreatic cancer cells [ 68 ]. The results demonstrated that BAIC at very low concentrations reduced the viability of cancer cells more than either AHCC or Wasabi used alone.…”

“…The results demonstrated that BAIC at very low concentrations reduced the viability of cancer cells more than either AHCC or Wasabi used alone. The anticancer activity of BAIC was mediated through increasing the G0/G1 population and augmenting the percentage of apoptotic cells by upregulating the expressions of pro-apoptotic proteins [ 68 ]. A study exploring the synergistic effects of combining the mushroom Agaricus bisporus and Shiitake ( Lentinus edodes ) on prostate cancer cells demonstrated significant reduction of IL-8, NFkB and nuclear to cytoplasmic ratio, suggesting an enhanced anticancer efficacy of this combined formulation [ 69 ].…”

Nutritional Modulation of the Immune Response Mediated by Nucleotides in Canine Leishmaniosis

“…This product was developed by Amino Up Chemical Co. Ltd. (Sapporo, Japan) in Japan in 1992. Several articles describe its therapeutic effects in both in vitro assays and in human and animal studies, including modulation of the immune response, antioxidant and anticancer activity, and prevention of infectious processes [179][180][181][182][183][184][185][186][187]. Leishmaniasis patients could benefit from some of these reported positive effects, such as increased Th1 cell responses [179][180][181], increased production of IL-17 and IFN-γ by CD4+ T cells [180], and modulation of the immune response in intestinal epithelial cells and macrophages [183].…”

From Quinoline to Quinazoline‐Based S. aureus NorA Efflux Pump Inhibitors by Coupling a Focused Scaffold Hopping Approach and a Pharmacophore Search

“…The cytotoxic effect of the compounds was determined by MTT assays performed on THP-1 and A549 (CCL-185TM) cells after 24 h exposure. [56] Cells were seeded at the density of 1 × 10 4 cells/well into 96-well flat-bottomed plates in 200 μL of RPMI medium and then exposed for 24 h to the compounds at the concentrations resulted synergistic in checkerboard assays. Unexposed cells were used as negative control.…”