Related Experiment Video
Updated: May 27, 2025
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Unveiling 2-isopropyl-5-methylphenol's immunomodulatory potential in breast cancer: A synergistic computational and
Mehr Un Nissa Bashir1, Muhammad Usman Rashid2, Naila Malkani1
1Department of Zoology, GC University, Lahore, Pakistan.
Abstract:
Tumor cells evade immune surveillance and promote their growth by modulating immune checkpoint molecules (ICMs). Various breast cancer subtypes have demonstrated the involvement of these molecules, promoting the investigation of natural compounds for immunomodulatory potential. 2-Isopropyl-5-methylphenol, a bioactive monoterpenoid found in several plant species, was evaluated for its impact on breast cancer immunomodulation. Computational and in-vitro studies were conducted to evaluate 2-Isopropyl-5-methylphenol's immunomodulatory potential. Molecular docking of ICMs (CTLA-4, PD-1, and PD-L1) with 2-Isopropyl-5-methylphenol was performed using AutoDock Vina. Additional tools utilized were BIOVIA Discovery Studio 2021, PyMOL, and LigPlot+. The mRNA expression of ICMs upon treatment of breast cancer cells (MDA-MB-231) with varying concentrations (50, 100, and 200 µg) of 2-Isopropyl-5-methylphenol was measured by qPCR. Docking complexes of CTLA-4, PD-1, and PD-L1 with 2-Isopropyl-5-methylphenol showed binding free energies of -4.3 kcal/mol, -5.2 kcal/mol and -4.4 kcal/mol, respectively. Involvement of different key amino acid residues strengthened 2-Isopropyl-5-methylphenol's binding with ICMs. Expression analysis revealed 2-Isopropyl-5-methylphenol downregulated CTLA-4 expression while upregulated PD-1 and PD-L1 expression. This study highlights the immunomodulatory potential of the bioactive monoterpene 2-Isopropyl-5-methylphenol. Supported by computational and in-vitro findings, 2-Isopropyl-5-methylphenol could be considered as a potential target for anti-tumor drug development.
Insights
2-Isopropyl-5-methylphenol shows potential for breast cancer treatment by modulating immune checkpoint molecules (ICMs). This natural compound impacts CTLA-4, PD-1, and PD-L1 expression, offering a new avenue for anti-tumor drug development.
Area of Science:
- Immunology
- Pharmacology
- Computational Biology
Background:
- Tumor cells evade immune surveillance by modulating immune checkpoint molecules (ICMs).
- Breast cancer subtypes involve ICMs, prompting research into natural compounds for immunomodulation.
- 2-Isopropyl-5-methylphenol is a bioactive monoterpenoid with potential immunomodulatory properties.
Purpose of the Study:
- To evaluate the immunomodulatory potential of 2-Isopropyl-5-methylphenol on breast cancer.
- To investigate the interaction between 2-Isopropyl-5-methylphenol and key immune checkpoint molecules (ICMs).
- To assess the effect of 2-Isopropyl-5-methylphenol on ICMs' mRNA expression in breast cancer cells.
Main Methods:
- Computational molecular docking of 2-Isopropyl-5-methylphenol with CTLA-4, PD-1, and PD-L1 using AutoDock Vina.
- In vitro studies involving treatment of MDA-MB-231 breast cancer cells with varying concentrations of 2-Isopropyl-5-methylphenol.
- Quantitative PCR (qPCR) to measure the mRNA expression of ICMs.
Main Results:
- Molecular docking revealed favorable binding free energies between 2-Isopropyl-5-methylphenol and CTLA-4 (-4.3 kcal/mol), PD-1 (-5.2 kcal/mol), and PD-L1 (-4.4 kcal/mol).
- Key amino acid residues were involved in the binding interactions, strengthening the compound's affinity.
- In vitro studies showed that 2-Isopropyl-5-methylphenol downregulated CTLA-4 mRNA expression while upregulating PD-1 and PD-L1 mRNA expression.
Conclusions:
- 2-Isopropyl-5-methylphenol exhibits significant immunomodulatory potential relevant to breast cancer.
- The compound's ability to modulate ICMs, supported by computational and in vitro data, suggests its therapeutic promise.
- 2-Isopropyl-5-methylphenol warrants further investigation as a potential candidate for anti-tumor drug development.
