Vitexin modifying the expression of APC, p53, KRAS genes with metabolome profile changes in HT-29 colorectal cancer cell line

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

الهام  قدوسی دهنوی ¹ (گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;)
رضا  حاجی حسینی ² (گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;)
محمد  ارجمند ³ (گروه بیوشیمی، انستیتو پاستور ایران، تهران، ایران;)
سیما  نصری ⁴ (گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران;)
زهرا  زمانی ⁵ (گروه بیوشیمی، انستیتو پاستور ایران، تهران، ایران;)

Received: 2022-12-25 Accepted : 2023-04-19 Published : 2023-05-22

Keywords: Colorectal cancer, Metabolomics, p53, APC, KRAS, Vitexin, 1HNMR,

Abstract :

Background & Aim: Colorectal canceris a clinically heterogeneous disease resulting from metabolome pattern alterations of many metabolites and their genetic factor interactions in man. Chemotherapy in colorectal cancer is generally followed by multiple side effects, including drug resistance; It is well established that herbal medicines are gaining worldwide interest in treating many cancers. Vitexin is an apigenin flavone glycoside present in hawthorn has exhibited therapeutic properties. This study was performed to assess the antitumor properties of Vitexin on the expression of p53, KRAS, and APC genes and the metabolome profile alterations associated with these genetic modifications.Experimental: Cells were treated with different concentrations of Vitexin, and toxicity and cell growth inhibition were ascertained in vitro using the MTT assay method. Cells were treated with Vitexin, and gene expression was determined. Following metabolome 1HNMR spectroscopy with 1D NOESY protocol and the resulting spectra scrutinized to classify differentiated metabolites and their biochemical pathways. Integrative systems biology analysis software examined the metabolites and the genes, and the main pathways modulated by gene expression were identified.Results: Our finding revealed that a 50% inhibitory concentration for Vitexin was 16.32 μM, while the relative expression of tumor suppressor genes APC and p53 in treated cells enhanced and the expression of the KRAS oncogene gene decreased significantly compared to the control group. The crucial changes in convergent metabolic phenotype with genes were identified in this investigation.Recommended applications/industries: Our findings revealed that Vitexin exhibits antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.

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