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杏鲍菇提取物诱导结直肠癌细胞凋亡。

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines.

机构信息

Laboratory of Genomics, Proteomics and DNA Repair, Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, Brazil; Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal.

Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal.

出版信息

Food Chem Toxicol. 2018 Feb;112:383-392. doi: 10.1016/j.fct.2018.01.015. Epub 2018 Jan 11.

Abstract

Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 and HTC116 cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 without cytotoxicity in HTC116 cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma.

摘要

姬松茸(PSC)是一种可食用的蘑菇,用于食品补充剂,通过诱导细胞死亡途径表现出抗肿瘤特性。通过将 HCT116 细胞暴露于不同的 PSC 提取物来分析 PSC 对结直肠癌的潜力。PSC 正己烷提取物(PSC-hex)显示出最高的细胞毒性作用(IC 值为 0.05mg/mL)。然后将观察到的细胞毒性与促进细胞凋亡和细胞周期阻滞途径相关联。PSC-hex 能够诱导与线粒体膜电位崩溃和 ROS 生成相关的细胞凋亡。在 HTC116 和 HTC116 细胞中没有观察到细胞毒性,同时 p53、Bax 和 Caspase-3 的表达增加,Bcl-2 的表达减少,这表明促凋亡作用可能是通过 p53 相关途径诱导的。PSC-hex 诱导 HCT116 细胞周期停滞在 G2/M 期,而在 HTC116 细胞中没有细胞毒性。这些发现表明,PSC-hex 中存在的化合物可能破坏了 p21/p53 细胞周期调节途径。然后用代表总重量 30.6%的麦角甾-5,7,22-三烯-3β-醇对主要成分进行了鉴定。对麦角甾-5,7,22-三烯-3β-βcl-2 进行了体外对接研究,结果表明与 Bcl-2 疏水裂缝具有可信的相互作用。结果表明,PSC-hex 可作为结直肠癌辅助治疗的补充食品。

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