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Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-01-11 , DOI: 10.1016/j.fct.2018.01.015
Tiane C. Finimundy , Rui M.V. Abreu , Natalia Bonetto , Fernando J. Scariot , Aldo J.P. Dillon , Sergio Echeverrigaray , Lillian Barros , Isabel C.F.R. Ferreira , João A.P. Henriques , Mariana Roesch-Ely

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 HCT116wt cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC50 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-p53 and HTC116-Bax 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 HCT116wt without cytotoxicity in HTC116-p21 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.



中文翻译:

杏鲍菇提取物对大肠癌细胞株的凋亡诱导作用

杏鲍菇(PSC)是一种食用蘑菇,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 wt细胞暴露于不同的PSC提取物中来分析针对大肠癌的PSC潜力。PSC正己烷提取物(PSC-hex)表现出最高的细胞毒性作用(IC 50值为0.05 mg / mL)。然后,观察到的细胞毒性与促进细胞凋亡和阻滞细胞周期的途径有关。PSC-hex能够诱导与线粒体膜电位破坏和ROS产生有关的凋亡。HTC116 -p53和HTC116 -Bax中没有细胞毒性细胞,以及p53,Bax和Caspase-3表达的增加以及Bcl-2表达的减少,都支持促凋亡作用可能是通过p53相关途径诱导的。PSC-六角诱导的细胞周期停滞在G2 / M在HCT116与wt无细胞毒性在HTC116 -p21 细胞。这些发现表明,p21 / p53细胞周期调控途径可能被PSC-hex上存在的化合物破坏。然后,使用占总重量30.6%的ergosta-5,7,22-trien-3β-ol进行主要成分的鉴定。在计算机对接研究中,ergosta-5、7、22-trien-3β与Bcl-2发生了对接,结果表明与Bcl-2疏水裂缝的相互作用是可信的。结果表明,PSC-hex可作为大肠癌辅助治疗的辅助食品。

更新日期:2018-01-11
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