Maitake (D Fraction) Mushroom Extract Induces Apoptosis in Breast Cancer Cells by BAK-1 Gene Activation

Abstract

For many years mushrooms have been used empirically in traditional medicine to treat several diseases. Study of the maitake mushroom, with its immunomodulatory and antitumoral properties, has led to the isolation of several bioactive compounds. One of these, D fraction, is known to reduce tumor cell viability. This study examined the effect of isolated D fraction on viability and apoptosis of human breast cancer cells (MCF7). These cells were treated with maitake (D fraction) extract at 18 μg/mL, 36 μg/mL, 91 μg/mL, 183 μg/mL, or 367 μg/mL or were left untreated (control) for 24 hours. MCF7 incubation with the maitake extract resulted in decreased cell viability [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay] in a dose-dependent manner. Apoptosis was statistically significantly increased in a dose-dependent manner at every concentration tested (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay). Upon incubation with D fraction, a microarray assay revealed upregulation of BAK-1 and cytochrome c transcripts, 2 proteins directly involved in the apoptotic pathway. Reverse transcriptase polymerase chain reaction studies confirmed these findings; BAK-1 was one of most overexpressed gene, as observed by microarray assay. These findings confirm the apoptotic effect of maitake D fraction in breast cancer cells and further highlight the involvement of cytochrome c release to the cytoplasm. Cytoplasmic release of cytochrome c, another player in the apoptotic pathway, was also increased after incubation with D fraction in a dose-dependent manner. This finding indicates that the effect of this compound involves mitochondrial dysfunction. The identification of the molecular mechanisms by which D fraction exerts its effects is crucial for the development of preventive and therapeutic strategies for cancer.

Genes Related to Suppression of Malignant Phenotype Induced by Maitake D-Fraction in Breast Cancer Cells

“…In our previous work, we have demonstrated that D-Fraction of Maitake mushroom was able to effectively induce apoptosis in MCF-7 breast cancer cells. 10 These findings were corroborated by a reduction in cell viability upon treatment with different concentrations of this fraction. Several genes promoting apoptosis were upregulated as assessed by cDNA microarray analysis.…”

Comparative Effect of Maitake Pro4x with Chemotherapy Breast Cancer Treatment

“…Thus, the Maitake D-fraction treatment alone may have a chemotherapeutic effect by inducing cell death in a dose-dependent manner. In previous studies, we demonstrated that tumour MCF-7 cell death was induced by Maitake Pro4X via apoptosis [36]. Moreover, were observed that treatment with chemotherapeutic drugs increased cell death at a higher level compared with treatment with the Maitake D-fraction.…”

“…As mentioned previously, the antitumor properties of the Maitake DFraction are attributed to its immunomodulatory effect. Reports have also indicated that Maitake directly induce apoptosis in tumour cells such as prostate [33], stomach [34], kidney [35] and breast [36] cancer cells.…”

Immunotherapeutic and Preventive Role of Purified Extract Rich in Beta-Glucans Derived from D-Fraction of Grifola frondosa Mushroom in Experimental Mice Biomodel of Mammary Carcinogenesis

“…So far, we have demonstrated that the treatment with Maitake D-Fraction Pro4X prevents the development of mammary tumorigenesis, blocks tumor invasiveness, reduce tumor angiogenesis, increases overall survival in animals, and exhibits selective cytotoxicity [24][25][26]. Moreover, we also demonstrated that the use of Maitake D-Fraction Pro4X is safe and nontoxic as well.…”