Targeting cell cycle arrest in breast cancer by phytochemicals from Caryto urens L. fruit ethyl acetate fraction: in silico and in vitro validation

Abstract

Background

Caryota urens, also known as Shivjata, has been documented in ancient Indian texts for its therapeutic benefits, addressing conditions from seminal weakness to gastric ulcers. This study aims to investigate its contemporary medicinal potential in treating breast cancer.

Objectives

The study focuses on exploring the therapeutic potential of Caryota urens fruit against breast cancer, specifically targeting cell cycle genes CDK1, CDC25A, and PLK1 through bioinformatics, network pharmacology, and in vitro validation.

Materials and methods

Using mass spectrometry and nuclear magnetic resonance (NMR), 60 key phytoconstituents from Caryota urens fruit were identified. Bioinformatics analysis, integrating Gene Cards and GEO databases, 15,474 breast cancer-associated genes focusing on the HR+/HER2-subtype were identified. Molecular docking and qPCR validated the interactions of key phytoconstituents, particularly Episesamin, with CDK1, CDC25A, and PLK1. In vitro studies were conducted on the MCF7 cell line, supplemented by ROC and survival analyses to evaluate diagnostic and therapeutic potential.

Results

The bioinformatics analysis identified CDK1, CDC25A, and PLK1 as pivotal genes regulating cell cycle progression and breast cancer tumorigenesis. Network pharmacology and in vitro studies indicated that phytoconstituents, especially Episesamin, downregulated these genes in breast cancer cells. Molecular docking and qPCR confirmed these interactions, and ROC and survival analyses underscored their diagnostic and therapeutic significance.

Conclusions

This study suggests that Caryota urens fruit extract, particularly Episesamin, may inhibit breast cancer metastasis by downregulating CDK1, CDC25A, and PLK1, offering promising new strategies for targeting the cell cycle in breast cancer and emphasizing the value of integrating bioinformatics with experimental methods in cancer research.