Anti-Cancer Effect of Dorema Ammoniacum Gum by Targeting Metabolic Reprogramming by Regulating APC, P53, KRAS Gene Expression in HT-29 Human Colon Cancer Cells.

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Elham Ghodousi-Dehnavi, Mohammad Arjmand, Ziba Akbari, Mansour Aminzadeh, Reza Haji Hosseini
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引用次数: 0

Abstract

Background: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.

Results: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.

Conclusion: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.

Dorema Ammoniacum口香糖通过调节HT-29人结肠癌癌症细胞APC、P53、KRAS基因表达靶向代谢再编程的抗癌作用。
背景:癌症是一种异质性疾病,由于多种上游遗传和分子变化和相互作用,导致代谢紊乱。新疗法的发展,特别是草药,受到了全球的广泛关注。多雷马是一种药用植物。它的口香糖用于治疗已知的疾病。基于核磁共振1HNMR作为一种非侵入性和可重复性工具研究代谢组谱,可以将代谢变化确定为细胞内流量的反映,尤其是在药物反应中。本研究旨在研究不同树胶提取物对HT-29细胞代谢变化的抗癌作用及其对基因表达的影响。方法:采用正己烷、三氯甲烷、二氯甲烷等有机溶剂提取多瑞玛氨胶。评估细胞抑制生长百分比和IC50。用二氯甲烷提取物处理细胞后,测定p53、APC和KRAS基因表达。进行1HNMR光谱分析。最终,系统生物学软件工具同时解释了组合代谢产物和基因。结果:测定的IC50浓度最低的是二氯甲烷溶剂,最高的是己烷和氯仿。与对照组相比,二氯甲烷提取物处理后KRAS癌基因的表达显著降低,抑癌基因p53和APC的表达显著增加。大多数基因改变了趋同代谢表型。结论:本研究结果表明,多瑞玛氨胶的二氯甲烷溶剂通过改变HT-29细胞中相关基因的表达以及由此引起的下游代谢重编程的变化,显示出其抗肿瘤特性。
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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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