Evaluation of Active Hexose Correlated Compound (AHCC) in Combination With Anticancer Hormones in Orthotopic Breast Cancer Models

Integr Cancer Ther. 2017 Sep;16(3):300-307. doi: 10.1177/1534735417704948. Epub 2017 Apr 25.


Objective: To determine the impact on antitumor activity when active hexose correlated compound (AHCC) in combination with anticancer hormonal agents in orthotopic mouse models of human estrogen receptor positive breast cancer and evaluate impact of AHCC on aromatase activity.

Methods: The study consisted of 7 treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75. Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg + tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 µg/mouse, or letrozole 10 µg/mouse. All treatments were administered daily by oral gavage for 12 weeks. Tumors were measured 3 times a week. In vitro estrone and 17β-estradiol enzyme immunoassay was used to evaluate aromatase activity.

Results: There was no difference in the activity with the combination of AHCC + tamoxifen compared with tamoxifen ( P = 0.29). In the ZR-75 model (catechol- O-methyltransferase [COMT] wild-type), there was no difference in activity with the letrozole + AHCC compared with letrozole. However, in the MCF-7 model (COMT variant), AHCC + letrozole resulted in a decrease in activity compared with letrozole ( P < 0.01). Immunoassay data suggested that AHCC is a potential inducer of aromatase activity. In both tumor models, there was cytotoxicity observed with AHCC compared with untreated ( P < 0.02).

Conclusion: AHCC did not change the activity of tamoxifen. AHCC may have some interaction with letrozole in patients with COMT variant genotype. AHCC had cytotoxicity that warrents additional studies to evaluate its potential role for consolidation/prevention of breast cancer.

Keywords: AHCC; breast cancer; drug interactions; letrozole; tamoxifen.

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Aromatase Inhibitors / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Estradiol / metabolism
  • Estrogen Antagonists / pharmacology
  • Female
  • Humans
  • Letrozole
  • MCF-7 Cells
  • Mice
  • Nitriles / pharmacology
  • Polysaccharides / pharmacology*
  • Tamoxifen / pharmacology
  • Triazoles / pharmacology


  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Nitriles
  • Polysaccharides
  • Triazoles
  • Tamoxifen
  • Estradiol
  • Letrozole
  • Active Hexose Correlated Compound