Exploring Mechanism of Actions for Eugenol and Beta-Caryophyllene to Combat Colorectal Cancer Chemotherapy Using Network Pharmacology

Abstract

This study explores the potential of essential oils, Eugenol (EUG), and Beta-Caryophyllene (BCP) in enhancing the efficacy of the chemotherapeutic drug 5-fluorouracil (5-FU) in treating metastatic colorectal cancer (CRC). Pharmacokinetic assessment through ADMET analysis indicates that EUG and BCP adhere to the rule of five with good bioavailability, ensuring their drug-likeness properties. The study employs a multitarget strategy to reduce drug dosage and enhance effectiveness, testing the compounds on the HCT116 human colorectal cancer cell line. MTT assay revealed in-vitro cytotoxic effects of EUG, BCP, and 5-FU, with a noteworthy reduction in IC50 values observed when combining the compounds, indicating synergistic effects (CI < 1) as depicted in the Fa-CI plot. Network pharmacology-based analysis of the compound-disease-target (C-D-T) network identifies 58, 24, and 49 target proteins for EUG, BCP, and 5-FU, respectively, in metastatic CRC. Venn diagram intersection reveals 11 common target proteins, and the merged C-D-T network highlights 84 target proteins, with 16 selected based on edge count, including HSP90AA1, IGF-1R, ESR1, and CASP3. Molecular docking studies indicate that EUG, BCP, and 5-FU effectively inhibit the core target protein HSP90AA1 within the C-D-T network, suggesting their potential as modulators for CRC metastasis. These findings propose a promising approach for developing drugs targeting specific proteins to mitigate metastasis in colorectal cancer.