Abstract
Isoorientin (ISO) is a flavonoid compound extracted from plant species. The goal of this study was to determine the potential antiproliferative effects of ISO in HT-29 human colorectal adenocarcinoma cell line in vitro, specifically on cell viability, apoptosis, and cell cycle pathways. The cytotoxic effect of ISO isolated from E. spectabilis was measured using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HT-29 cell lines. Total RNA was isolated using Tri-Reagent protocol. The effects of ISO on apoptosis-related gene were detected using real-time polymerase chain reaction (RT-PCR). The findings were analyzed using "Delta-Delta CT" ΔΔCT method and evaluated using a computer program. Volcano plot analysis was used for comparing groups and the data obtained were statistically analyzed using Student t test. According to XTT result analysis, the 50% inhibitory concentration (IC50) value of ISO was 125 μM at the 48th h in HT-29 cells. The RT-PCR analysis in HT-29 cells showed that Cyclin D1 (CCND1 ), Cyclin-dependent kinase 6 (CDK6), BAX, BCL-2, Checkpoint kinase 1-2 (CHEK1, CHEK2) and Excision repair cross-complementing 1 (ERCC1) expressions were reduced in ISO-treated cells compared with those in the control group of cells. P53, P21, Caspase-3 (CASP-3), Caspase-8 (CASP-8), and Caspase-9 (CASP-9) gene expressions were increased Ataxia Telengiectasia and Rad-3 related (ATR) was activated in the ISO-treated group of cells compared with those in the control group of cells (p<0.05). ISO affected the proliferation of colorectal cancer (CRC) cells via cell cycle pathways. It also altered apoptosis gene expression. These results demonstrated that ISO can be a therapeutic agent for CRC treatment; however, more studies are needed to investigate its mechanism of actions.
Highlights
Cancer is a serious health problem worldwide, with rising life expectancy and changing environmental conditions as well as lifestyle
The real-time polymerase chain reaction (RT-PCR) analysis in HT-29 cells showed that Cyclin D1 (CCND1 ), Cyclin-dependent kinase 6 (CDK6), BAX, BCL-2, Checkpoint kinase 1-2 (CHEK1, CHEK2) and Excision repair cross-complementing 1 (ERCC1) expressions were reduced in ISO-treated cells compared with those in the control group of cells
Effects of ISO on Cell Cycle-associated Gene Proteins RT-PCR analysis in the present study demonstrated that ISO-treated HT-29 cells significantly decreased CCND1 and CDK6 expressions with respect to the control group cells (p
Summary
Cancer is a serious health problem worldwide, with rising life expectancy and changing environmental conditions as well as lifestyle. Cancer causes genetic alterations following failure of homeostatic mechanisms [1]. A large number of changes in gene expression leading to unregulated control of cell proliferation may result in tumor formation. Altered gene expression, of oncogenes and tumor suppressor genes, plays a key role in carcinogenesis [3]. CRC is the more prevalent form of lower gastrointestinal cancer, and about 75% of CRC cases are associated with environmental factors and nutrition. The remaining 25% cases have a hereditary CRC association among family members [4]. CRC, with more than a million of new cases per year, has few treatment options especially for advanced and metastatic patients
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