Maitake mushroom extract induce apoptosis in breast cancer cells by BAK-1 gene activation.

RAQUEL SOARES; MANUELA MEIRELES; ANA ROCHA; ANA PIRRACO; DIEGO OBIOL; ELIANA ALONSO; GISELA JOOS; GABRIELA BALOGH

JOURNAL OF MEDICINAL FOOD

MARY ANN LIEBERT INC

Lugar: New York; Año: 2011 vol. 20 p. 1 - 10

1096-620X

Mushrooms have been used empirically in traditional medicine for the treatment of several diseases for many years. The Maitake mushroom with its immunomodulatory and anti-tumoral properties has provided the isolation of several bioactive compounds. One of these, fraction-D, is known to reduce tumor cell viability. This study examined the effect of isolated D-fraction, directly on human breast cancer cells (MCF7) viability and apoptosis. MCF7 cells were treated with Maitake (D-Fraction) extract at 18 µg/mL, 36 µg/mL, 91 µg/mL, 183 µg/mL, 367 µg/mL or left untreated (Control) for 24 hours. MCF7 incubation with the Maitake extract resulted in decreased cell viability (MTS assay) in a dose-dependent manner. Apoptosis was significantly increased in a dose-dependent manner at every concentration tested (TUNEL assay). Upon incubation with D-fraction, microarray assay revealed an up-regulation of BAK-1 and cytochrome c transcripts, two proteins directly involved in the apoptotic pathway. RT-PCR 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. An increased cytoplasmic release of cytochrome c, another player in the apoptotic pathway, was also observed after incubation with D-fraction in a dose-dependent manner, emphasizing that the effect of this compound involves a 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 against cancer.