Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice

Abstract

BACKGROUND/OBJECTIVESA variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown.MATERIALS/METHODSIn the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU (10 mg·kg-1·d-1, i.p), or AHCC (360 mg·kg-1·d-1, i.g) plus 5-FU, respectively, for 5 d. CD3+, CD4+, CD8+, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and TNFα in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR.RESULTSDiet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of CD3+, CD4+, and NK cells (P < 0.01), and ratio of CD4+/CD8+ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and TNFα compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01).CONCLUSIONSThese results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

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

“…34 On the other hand, no significant differences have been noticed in cell cycle distribution following the treatment with AHCC, which is consistent with its role as coadjutant of antitumorigenic therapies than as single agent. 25,35,36…”

MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC)

“…AHCC has proven to be effective in reducing tumor growth and metastasis in animal models, particularly when combined with a conventional therapy. 5,43,44 Therefore, we aimed to study the underlining mechanisms that drive the anti-carcinogenic effects of AHCC and its relationship to the Cancer Stem Cell Theory in Breast Cancer Stem Cells (BCSCs). 45 Since current therapies do not target CSCs, it is important to conduct research on possible alternative therapies.…”

The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies

“…The beneficial effect of AHCC® on murine B16 melanoma is further supported by a recent study reporting decreased melanoma sizes in mice supplemented with AHCC® with or without CpGoligodeoxynucleotide (ODN), which is known to activate innate immunity and serve as an immunologic adjuvant [18]. The antitumor effects of low-dose 5-fluorouracil (5-FU) were potentiated by AHCC® in hepatoma 22 tumor-bearing mice through modulation of immune function, including increased percentages of NK cells [13]. However, no significant difference in NK cell activity was found between healthy human volunteers who took AHCC® (3 g/day × 4 weeks) and placebo, which could be related to small sample sizes (n = 10 and 11 for AHCC® and placebo groups, respectively) [26].…”

“…The effect of AHCC® on CD4 + T cells was found in hepatoma 22 tumor-bearing mice [13]. Compared to mice treated with 5-FU, mice treated with 5-FU and AHCC® had an increase in the percentage of CD4 + T cells and levels of Journal of Immunology Research IL-2, the T cell growth factor, in peripheral blood [13]. This observation raises the possibility that the antitumor effect of AHCC® can be mediated in part by modulating T cell function.…”

“…Of the oligosaccharides in AHCC®, about 20% are α-1,4-glucans, of which a proportion is partially acylated, with a mean molecular weight around 5000 Daltons [6,7]. The effects of AHCC® on immune cells of humans and animals were reported in in vitro and in vivo studies, suggesting the possible help of its supplementation in defending the host against infections and malignancies via modulating the immune system [6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This review focuses on the reported effects of AHCC® on natural killer (NK) and T cells given their roles in host defense and inflammation [29][30][31][32][33][34], providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC® and possibly other medical mushrooms in health and disease.…”