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Sudha Gahlawat, Panjab UniversityFollow

Presenting Author

Sudha Gahlawat

Presentation Type

Poster

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Cytochrome P450 (CYPs) belongs to Phase I enzymes and exists in multiple isoforms. CYPs are present in all tissues with the highest concentrations in the liver and small intestine. These are mainly involved in drug detoxification, cellular homeostasis, metabolism of endogenous & exogenous substrates and in the inactivation/ activation of several anticancer drugs. As these CYPs are selectively and differentially expressed in CRC, which could not only provide a mechanism for drug resistance, but also insights into future therapies that may use these enzymes as therapeutic targets. This study is designed to evaluate the differential expression of various CYPs isoforms in colorectal cancer (CRC) and their further modulation via phytochemicals using in silico approach. CRC differential expression data was downloaded from TCGA database, using the Broad Institute’s firehose_get data-retrieval utility. DEApp tool, was used to carry out differential expression analysis. Three CYPs were found to be differentially expressed in colorectal cancer. Isoforms with downregulated expressions were CYP3A4, and CYP4B1 having fold change values of -6.1262, and -4.8293 respectively. However, the expression of CYP2W1 was upregulated with a fold change value of 8.39. Phytochemicals are known modulators of cytochrome P450’s expression and activity. The present study was focused on modulating CYPs activity using phytochemicals. Molecular docking studies were conducted using Autodock vina. Phytochemicals were taken from three repositories: PDTDB, Serpentina, and Phytochemica and a list of phytochemicals was screened using in silico approach based on their binding affinity. The phytochemicals with binding affinity >-7 were taken into account. The common phytochemicals that were discovered to modulate all three cytochrome P450’ s were rutin, swertiaside, and astragalin.

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Assessment of cytochrome P450 isoforms in colorectal cancer and utilization of phytochemicals for their modulation.

Cytochrome P450 (CYPs) belongs to Phase I enzymes and exists in multiple isoforms. CYPs are present in all tissues with the highest concentrations in the liver and small intestine. These are mainly involved in drug detoxification, cellular homeostasis, metabolism of endogenous & exogenous substrates and in the inactivation/ activation of several anticancer drugs. As these CYPs are selectively and differentially expressed in CRC, which could not only provide a mechanism for drug resistance, but also insights into future therapies that may use these enzymes as therapeutic targets. This study is designed to evaluate the differential expression of various CYPs isoforms in colorectal cancer (CRC) and their further modulation via phytochemicals using in silico approach. CRC differential expression data was downloaded from TCGA database, using the Broad Institute’s firehose_get data-retrieval utility. DEApp tool, was used to carry out differential expression analysis. Three CYPs were found to be differentially expressed in colorectal cancer. Isoforms with downregulated expressions were CYP3A4, and CYP4B1 having fold change values of -6.1262, and -4.8293 respectively. However, the expression of CYP2W1 was upregulated with a fold change value of 8.39. Phytochemicals are known modulators of cytochrome P450’s expression and activity. The present study was focused on modulating CYPs activity using phytochemicals. Molecular docking studies were conducted using Autodock vina. Phytochemicals were taken from three repositories: PDTDB, Serpentina, and Phytochemica and a list of phytochemicals was screened using in silico approach based on their binding affinity. The phytochemicals with binding affinity >-7 were taken into account. The common phytochemicals that were discovered to modulate all three cytochrome P450’ s were rutin, swertiaside, and astragalin.

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