Polyphenols From Morchella sextelata Induce Apoptosis of Colorectal Cancer Cells Through ROS-Mediated Endogenous Mitochondrial Apoptosis Pathway In Vitro

IF 3.5 2区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Feihong Zhai, Yan Wang, Miaoqing Yan
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引用次数: 0

Abstract

Colorectal cancer (CRC) is a common malignancy of the digestive tract. Although chemotherapy is considered the most effective method for the treatment of CRC, these drugs have significant side effects. The identification of antitumour active ingredients with high efficiency and fewer toxic side effects from natural products is important. The effects of polyphenols from artificially cultivated Morchella sextelata (MSP) on CRC were analysed at the cellular level. The antiproliferative and proapoptotic effects of MSP on HCT 116 and HT-29 CRC cells were determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a colony formation assay, morphological observation and flow cytometry. The anti-CRC effects and their molecular mechanism were subsequently explored by RT-qPCR, Western blotting, mitochondrial membrane potential assays, reactive oxygen species (ROS) level assays and antioxidant enzyme system assays. MSP had dose-dependent cytotoxic effects as revealed by the inhibition of colony formation and induction of morphological changes and apoptosis in HCT 116 and HT-29 cells. The RT-qPCR results revealed that MSP treatment decreased the expression of Bcl-2 and upregulated the expression of Bax, caspase-3 and caspase-9, which were verified by Western blot experiments. Furthermore, MSP led to the destruction of the mitochondrial membrane potential, which suggested that MSP induced mitochondria-mediated apoptosis in these two cell types. In addition, treatment with MSP increased ROS levels and reduced the levels of the antioxidant enzymes glutathione peroxidase (GSH-Px), glutathione S-transferase (GSH-ST) and γ-glutamylcysteine synthetase (γ-GCS) in the two cell lines. The apoptotic effects induced by MSP were significantly reversed by the ROS inhibitor N-acetyl-L-cysteine (NAC), indicating that MSP induced apoptosis by increasing the intracellular ROS content of these two cell types. The above results indicated that MSP induced the apoptosis in the CRC cell lines HCT 116 and HT-29 through the ROS-mediated endogenous mitochondrial apoptosis pathway. The conclusions drawn from these experiments were based on in vitro cell experiments, and the results of this study provide a research basis for further in-depth experiments.

Abstract Image

六鳃羊肚菌多酚通过ros介导的内源性线粒体凋亡途径诱导结直肠癌细胞凋亡
结直肠癌(CRC)是一种常见的消化道恶性肿瘤。虽然化疗被认为是治疗结直肠癌最有效的方法,但这些药物有明显的副作用。从天然产物中鉴定出高效、毒副作用小的抗肿瘤活性成分十分重要。从细胞水平分析了人工培养羊肚菌(MSP)多酚对结直肠癌的影响。采用3-(4,5-二甲基噻唑-2-酰基)-2,5-二苯基溴化四唑(MTT)实验、菌落形成实验、形态学观察和流式细胞术检测MSP对HCT 116和HT-29 CRC细胞的抗增殖和促凋亡作用。随后通过RT-qPCR、Western blotting、线粒体膜电位测定、活性氧(ROS)水平测定和抗氧化酶系统测定探讨其抗crc作用及其分子机制。通过抑制HCT 116和HT-29细胞的集落形成、诱导细胞形态变化和凋亡,发现MSP具有剂量依赖性的细胞毒作用。RT-qPCR结果显示,MSP处理降低了Bcl-2的表达,上调了Bax、caspase-3和caspase-9的表达,Western blot实验证实了这一点。此外,MSP导致线粒体膜电位的破坏,这表明MSP在这两种细胞类型中诱导了线粒体介导的凋亡。此外,MSP处理增加了两种细胞系的ROS水平,降低了抗氧化酶谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽s -转移酶(GSH-ST)和γ-谷氨酰半胱氨酸合成酶(γ-GCS)的水平。ROS抑制剂n -乙酰半胱氨酸(N-acetyl-L-cysteine, NAC)显著逆转了MSP诱导的凋亡作用,表明MSP通过增加这两种细胞的胞内ROS含量诱导凋亡。上述结果表明,MSP通过ros介导的内源性线粒体凋亡途径诱导CRC细胞株HCT 116和HT-29凋亡。这些实验得出的结论均基于体外细胞实验,本研究结果为进一步深入实验提供了研究基础。
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来源期刊
Journal of Food Biochemistry
Journal of Food Biochemistry 生物-生化与分子生物学
CiteScore
7.80
自引率
5.00%
发文量
488
审稿时长
3.6 months
期刊介绍: The Journal of Food Biochemistry publishes fully peer-reviewed original research and review papers on the effects of handling, storage, and processing on the biochemical aspects of food tissues, systems, and bioactive compounds in the diet. Researchers in food science, food technology, biochemistry, and nutrition, particularly based in academia and industry, will find much of great use and interest in the journal. Coverage includes: -Biochemistry of postharvest/postmortem and processing problems -Enzyme chemistry and technology -Membrane biology and chemistry -Cell biology -Biophysics -Genetic expression -Pharmacological properties of food ingredients with an emphasis on the content of bioactive ingredients in foods Examples of topics covered in recently-published papers on two topics of current wide interest, nutraceuticals/functional foods and postharvest/postmortem, include the following: -Bioactive compounds found in foods, such as chocolate and herbs, as they affect serum cholesterol, diabetes, hypertension, and heart disease -The mechanism of the ripening process in fruit -The biogenesis of flavor precursors in meat -How biochemical changes in farm-raised fish are affecting processing and edible quality
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