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

محورهای موضوعی : مجله گیاهان دارویی

Elham Ghodousi-Dehnavi ¹ , Reza Haji Hosseini ² , Mohammad Arjmand ³ , Sima Nasri ⁴ , Zahra Zamani ⁵

1 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
2 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
3 - Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran;
4 - Department of Biology, Payame Noor university (PNU), P. OBox 19395-4697, Tehran, Iran;
5 - Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran;

تاریخ دریافت : 1401/10/04 تاریخ پذیرش : 1402/01/30 تاریخ انتشار : 1402/03/01

کلید واژه: Colorectal cancer, Metabolomics, p53, APC, KRAS, Vitexin, 1HNMR,

چکیده مقاله :

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.

چکیده انگلیسی:

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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