The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia, Sinica, Taichung 404, Taiwan.
Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University, Hospital, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2019 Feb 15;20(4):833. doi: 10.3390/ijms20040833.
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. (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.
在过去几十年中，随着检查技术的最新进展，乳腺癌的报告病例数量急剧增加。乳腺癌已成为全球女性死亡的第二大主要原因，促使科学界从天然来源开发或寻找具有强大活性和合理安全性的新药物，以应对这一疾病。(AC)是一种珍贵的药用真菌，由于其强大的保肝和细胞毒性活性而引起关注。我们评估了人工培养 AC 的乙醇提取物（EEAC）对体内和体外乳腺癌细胞（T47D 细胞）的抗增殖活性。人工培养 AC 的乙醇提取物通过将细胞周期阻滞在 G1 期来抑制 T47D 细胞的增殖，并诱导自噬。免疫印迹分析证实，EEAC 不仅降低了细胞周期相关蛋白的表达，还增加了转录因子 FOXO1、自噬标志物 LC3 II 和 p62 的表达。乙醇提取物通过促进 IRE1（肌醇需求酶 1α）、GRP78/Bip（葡萄糖调节蛋白 78）和 CHOP（C/EBP 同源蛋白）的表达来介导内质网应激。除了之前的研究外，还通过无细胞系统、免疫印迹和免疫荧光测定证实 EEAC 抑制了组蛋白去乙酰化酶（HDACs）的活性。体内研究表明，EEAC 可降低肿瘤体积并抑制肿瘤生长，而没有任何明显的副作用。高效液相色谱图谱显示，与野生 AC 乙醇提取物的图谱相比，EEAC 具有相似的三萜类化合物。EEAC 对乳腺癌细胞的多种作用靶点表明，这种提取物可能被开发为针对这种衰弱性疾病的潜在膳食补充剂。
