Reported cases of breast cancer have skyrocketed in the last decades with recent advances in examination techniques. Brest cancer has become the second leading cause of mortality among women worldwide, urging the scientific community to develop or find new drugs from natural sources with potent activity and a reasonable safety profile to tackle this ailment. Antrodia cinnamomea (AC) is a treasured medicinal fungus which has attracted attention due to its potent hepatoprotective and cytotoxic activities. We evaluated the antiproliferative activity of the ethanol extract of artificially cultured AC (EEAC) on breast cancer cells (T47D cells) in vivo and in vitro. Ethanol extract of artificially cultured AC inhibited T47D cells' proliferation mediated by cell cycle arrest at G1 phase as well induced autophagy. Immunoblotting assay confirmed that EEAC not only decreased the expression of the cell-cycle-related proteins but also increased the expression of transcription factor FOXO1, autophagic marker LC3 II, and p62. Ethanol extract of artificially cultured AC mediated endoplasmic reticulum stress by promoting the expression of IRE1 (inositol-requiring enzyme 1α), GRP78/Bip (glucose regulating protein 78), and CHOP (C/EBP homologous protein). Apart from previous studies, HDACs (histone deacetylases) activity was inhibited as demonstrated by a cell-free system, immunoblotting, and immunofluorescence assays following EEAC treatment. The in vivo studies demonstrated that EEAC decreased tumor volume and inhibited tumor growth without any significant side effects. High performance liquid chromatography profile demonstrated similar triterpenoids compared to the profile of wild AC ethanol extract. The multiple targets of EEAC on breast cancer cells suggested that this extract may be developed as a potential dietary supplement targeting this debilitating disease.
Keywords: Antrodia cinnamomea; breast cancer; endoplasmic reticulum stress; histone deacetylases.