High-throughput sequencing reveals <i>Jatrorrhizine</i> inhibits colorectal cancer growth by ferroptosis-related genes

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Abstract

Background

Colorectal cancer is a malignant tumor that poses a serious threat to human health. The main objective of this study is to investigate the mechanism by which Jatrorrhizine (JAT), a root extract from Stephania Epigaea Lo, exerts its anticancer effects in colorectal cancer.

Methods

We initially assessed the inhibitory properties of JAT on SW480 cells using MTT and cell scratch assays. Flow cytometry was employed to detect cell apoptosis. Differentially expressed genes were identified through high-throughput sequencing, and they were subjected to functional enrichment and signaling pathway analysis and PPI network construction. RT-qPCR was used to evaluate gene expression and identify critical differentially expressed genes. Finally, the function and role of differentially expressed genes produced by JAT-treated SW480 cells in colorectal cancer will be further analyzed using the TCGA database.

Results

Our study demonstrated that JAT exhibits inhibitory effects on SW480 cells at concentrations of 12.5µM, 25µM, 50µM, and 75µM without inducing cell apoptosis. Through high-throughput sequencing, we identified 244 differentially expressed genes. KEGG and GO analysis of high-throughput sequencing results showed that differentially expressed genes were significantly enriched in MAPK, Wnt, and P53 signaling pathways. Notably, JAT significantly altered the expression of genes associated with ferroptosis. Subsequent RT-qPCR showed that the expression of ferroptosis genes SLC2A3 and ASNS was significantly lower in JAT-treated SW480 cells than in the control group. Analysis by TCGA data also showed that ferroptosis genes SLC2A3 and ASNS were significantly highly expressed in COAD. The prognosis of SLC2A3 was significantly worse in COAD compared to the normal group. SLC2A3 may be a core target of JAT for the treatment of COAD.

Conclusions

JAT can inhibit COAD growth by ferroptosis-related genes. And it is a potential natural substance for the treatment of COAD.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12920-023-01619-3.

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Most cited references 21

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Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Scott J. Dixon, Kathryn Lemberg, Michael Lamprecht … (2012)

Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.

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Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays

Tim R. Mosmann (1983)

A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.

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Targeting Ferroptosis to Iron Out Cancer

Behrouz Hassannia, Peter Vandenabeele, Tom Vanden Berghe (2019)

One of the key challenges in cancer research is how to effectively kill cancer cells while leaving the healthy cells intact. Cancer cells often have defects in cell death executioner mechanisms, which is one of the main reasons for therapy resistance. To enable growth, cancer cells exhibit an increased iron demand compared with normal, non-cancer cells. This iron dependency can make cancer cells more vulnerable to iron-catalyzed necrosis, referred to as ferroptosis. The identification of FDA-approved drugs as ferroptosis inducers creates high expectations for the potential of ferroptosis to be a new promising way to kill therapy-resistant cancers.

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Author and article information

Contributors

Lingyu Huang: huanglingyu99@163.com

Yu Sha: ShaYu_Elena@163.com

Wenken Liang: wenken199510@163.com

Chune Mo: cemo@glmc.edu.cn

Chunhong Li: 842567961@qq.com

Yecheng Deng: dyecheng@163.com

Weiwei Gong: vivian.gong@163.com

Xianliang Hou: houxl115@126.com

Minglin Ou: minglinou@163.com , minglinou@glmc.edu.cn

Journal

Journal ID (nlm-ta): BMC Med Genomics

Journal ID (iso-abbrev): BMC Med Genomics

Title: BMC Medical Genomics

Publisher: BioMed Central (London )

ISSN (Electronic): 1755-8794

Publication date (Electronic): 14 September 2023

Publication date PMC-release: 14 September 2023

Publication date Collection: 2023

Volume: 16

Electronic Location Identifier: 217

Affiliations

[1 ]GRID grid.443385.d, ISNI 0000 0004 1798 9548, Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, , The Second Affiliated Hospital of Guilin Medical University, ; Guilin, 541000 China

[2 ]GRID grid.459584.1, ISNI 0000 0001 2196 0260, Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, College of Life Science, , Ministry of Education of China, Guangxi Normal University, ; Guilin, 541000 China

Article

Publisher ID: 1619

DOI: 10.1186/s12920-023-01619-3

PMC ID: 10500743

PubMed ID: 37710311

SO-VID: 0cd70d91-fcd5-4d1e-839e-20f46c274a60

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 16 May 2023

Date accepted : 30 July 2023

Funding

Funded by: Science and Technology Plan of Guilin

Award ID: 20220139-8-4

Funded by: Guangxi Medical and health key cultivation discipline construction project

Funded by: Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders

Award ID: 19-xkjs-05

Custom metadata

ScienceOpen disciplines: Genetics

Keywords: jatrorrhizine,colorectal cancer,high-throughput sequencing,ferroptosis

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ScienceOpen disciplines: Genetics

Keywords: jatrorrhizine, colorectal cancer, high-throughput sequencing, ferroptosis

High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

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G3: Genes|Genomes|Genetics

Most cited references 21

Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays

Targeting Ferroptosis to Iron Out Cancer

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