Tumor suppressor p53 independent apoptosis in HT-29 cells by auransterol from Penicillium aurantiacobrunneum.
Tumor suppressor p53 independent apoptosis in HT-29 cells by auransterol from Penicillium aurantiacobrunneum.
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DOI：
10.1016/j.biopha.2020.110124
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Carcache de Blanco EC
中科院分区：
文献类型：
--
作者：
Anaya-Eugenio GD;Tan CY;Rakotondraibe LH;Carcache de Blanco EC
结直肠癌是美国癌症相关死亡的第三大原因。寻找治疗这种癌症的新方法是必要的。在先前的报告中，来自橙色青霉菌的橙色甾醇在HT-29癌细胞中显示出细胞毒性。因此，本研究的目的是研究橙甾醇在HT-29细胞中的潜在细胞毒性机制。使用SRB测定法在HT-29结肠癌细胞中测定橙甾醇的实时细胞毒性。分析MTP的丢失、ROS的过度产生、细胞周期、细胞迁移和半胱天冬酶活性。蛋白质印迹分析用于评估蛋白质表达。橙甾醇以时间和浓度依赖性方式降低细胞增殖率，在处理24、48和72 h时的IC 50值分别> 100、49.1和23.8 μM。与对照组相比，50 μM橙甾醇处理24 h后，HT-29细胞中MTP丢失，ROS过量产生，caspase活性增加，诱导细胞周期G1期积累和迁移抑制。这些结果得到Cyt c、BAX、PARP-1、p21和半胱氨酸天冬氨酸蛋白酶原-3蛋白上调以及Bcl-2下调而半胱氨酸天冬氨酸蛋白酶原-7和p53无修饰的支持。橙甾醇对HT-29结肠癌细胞的细胞毒性作用是通过线粒体凋亡介导的，而不依赖于p53激活、细胞周期G1期阻滞和细胞迁移抑制。这项工作鼓励进一步的临床前和临床研究的橙甾醇，并建议橙甾醇作为一个很好的候选人治疗结直肠癌。
Colorectal cancer is the third leading cause of cancer related-death in the United States. Search for new alternatives to treat this type of cancer is necessary. In a previous report, auransterol from Penicillium aurantiacobrunneum showed cytotoxicity in HT-29 cancer cells. Thus, the goal of this study was to examine the potential cytotoxic mechanism of auransterol in HT-29 cells. Real-time cytotoxicity of auransterol was determined in HT-29 colon cancer cells, using the SRB assay. Loss of MTP, overproduction of ROS, cell cycle, cell migration, and caspase activity were analyzed. Western blot analysis was used to evaluate protein expression. Auransterol reduced cell proliferation rate in a time and concentration-dependent manner, with an IC50 value > 100, 49.1 and 23.8 μM at 24, 48 and 72 h of treatment, respectively. After 24 h of treatment, 50 μM of auransterol induced loss of MTP, overproduction of ROS, increased caspase activity, induced cell cycle G1-phase accumulation and inhibition of migration in HT-29 cells compared to control. These results were supported by protein upregulation of Cyt c, BAX, PARP-1, p21 and procaspase-3, and downregulation of Bcl-2 with no modifications in procaspase-7 and p53. The cytotoxic effect of auransterol in HT-29 colon cancer cells is mediated by mitochondrial apoptosis independent of p53 activation, cell cycle G1 phase arrest, and inhibition of cell migration. This work encourages further preclinical and clinical studies of auransterol and suggests auransterol as a good candidate for colorectal cancer treatment.
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影响因子：
12.4
作者：
Kale J;Osterlund EJ;Andrews DW
通讯作者：
Andrews DW
DOI：
10.1080/01635581.2015.1087042
发表时间：
2015-11-17
影响因子：
2.9
作者：
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5.4
作者：
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通讯作者：
Wielgosz-Collin, Gaetane
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影响因子：
9
作者：
Liu K;Chen W;Lei S;Xiong L;Zhao H;Liang D;Lei Z;Zhou N;Yao H;Liang Y
通讯作者：
Liang Y
影响因子：
7.5
作者：
Bravo-Cordero, Jose Javier;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John