Antrodia cinnamomea, a Treasured Medicinal Mushroom, Induces Growth Arrest in Breast Cancer Cells, T47D Cells: New Mechanisms Emerge

Abstract

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.

Antrodia cinnamomea is a potentially effective complementary medicine for adjuvant therapy against breast cancer with bone metastasis

“…A study showed that autophagy of BC T47D cells was observed in vitro after treatment with ethanol extract of AC at a higher concentration (50 μg/mL) due to potent inhibition of CDK2 and CDK4. [ 19 ] In addition, the inhibition of histone deacetylase activity was observed after treatment with ethanol extract of AC. [ 19 ] Another study showed that 50 μg/mL ethanol extract of AC fruiting bodies containing 2 major compounds (dehydrosulfurenic acid and dehydroeburicoic acid) attenuated T47D BC cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators (including CDK 4, CDK 6, cyclin B1, cyclin D3, retinoblastoma protein (Rb), and phosphorylated Rb), and inducing apoptosis.…”

“…[ 19 ] In addition, the inhibition of histone deacetylase activity was observed after treatment with ethanol extract of AC. [ 19 ] Another study showed that 50 μg/mL ethanol extract of AC fruiting bodies containing 2 major compounds (dehydrosulfurenic acid and dehydroeburicoic acid) attenuated T47D BC cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators (including CDK 4, CDK 6, cyclin B1, cyclin D3, retinoblastoma protein (Rb), and phosphorylated Rb), and inducing apoptosis. [ 20 ] In fact, there are 2 major components, dehydrosulfurenic acid and dehydroeburicoic acid, in the AC supplied for the patient in this case report.…”

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials

“…The extract also mediated endoplasmic reticulum stress by upregulating the expression of inositol-requiring enzyme 1-α (IRE1), glucose-regulating protein 78 GRP78/Bip, and C/EBP homologous protein CHOP. Tumor growth was inhibited in vivo [ 51 ].…”

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

“…Previous studies have found AC mycelium (ACM) provides many beneficial pharmacological activities including anti-inflammation [ 3 ], anti-obesity [ 4 ], anti-cancer [ 5 ], reduction of mild hypertension [ 6 ] and improvement of nonalcoholic steatohepatitis [ 7 , 8 ]. Ethanolic extract of AC contains several bioactive constituents which display promising anti-tumor effects in several types of cancers [ 9 , 10 , 11 ]. A purified derivative of maleic and succinic acid, YMGKI-1, was previously discovered in those ACM ethanolic extracts which have shown inhibition in the stemness of head and neck cancer initiating cells both in vitro and in vivo [ 12 ].…”