Polyphenols From Morchella sextelata Induce Apoptosis of Colorectal Cancer Cells Through ROS-Mediated Endogenous Mitochondrial Apoptosis Pathway In Vitro
{"title":"Polyphenols From Morchella sextelata Induce Apoptosis of Colorectal Cancer Cells Through ROS-Mediated Endogenous Mitochondrial Apoptosis Pathway In Vitro","authors":"Feihong Zhai, Yan Wang, Miaoqing Yan","doi":"10.1155/jfbc/7777790","DOIUrl":null,"url":null,"abstract":"<div>\n <p>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 <i>Morchella sextelata</i> (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 <i>Bcl-2</i> and upregulated the expression of <i>Bax, caspase-3</i> and <i>caspase-9</i>, 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.</p>\n </div>","PeriodicalId":15802,"journal":{"name":"Journal of Food Biochemistry","volume":"2025 1","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/jfbc/7777790","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Food Biochemistry","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/jfbc/7777790","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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