In-silico study of rosmarinic acid roles in inhibiting breast cancer progression

TL;DR

This study uses computer simulations to explore how rosmarinic acid might help fight breast cancer by interacting with key proteins involved in its progression.

Contribution

The study identifies specific proteins targeted by rosmarinic acid in breast cancer using in-silico methods.

Findings

Rosmarinic acid binds to active sites of MMP-1, MMP-2, MMP-9, and MMP-12 proteins.

Rosmarinic acid shows similar binding to aldose reductase as known inhibitors.

Rosmarinic acid interacts with CDC25B in the same region as CDKs.

Abstract

Breast cancer is the highest cancer incidence in the world. Chemotherapy is currently one of the main breast cancer treatments besides surgery. It is capable of evolving to become resistant to chemotherapy agents. Chemotherapy also has significant side effects. Rosmarinic acid could become an anti-cancer agent candidate for the treatment of breast cancer, but its molecular mechanism is still unclear.

This study aimed to clarify the molecular mechanism of rosmarinic acid anti-breast cancer properties via an in-silico study.

Web-based screening tools such as SwissTargetPrediction, Similarity Ensemble Approach (SEA), and TargetNet were used as initial screening. From web-based screening, potential proteins that interact with rosmarinic acid could be determined. Intersected proteins from 3 web-based screenings were assessed via literature review. We found 11 intersected proteins, and 6 of 11 proteins are involved in breast cancer development and progression. Those 6 proteins are MMP-1, MMP-2, MMP-9, MMP-12, aldose reductase, and M-phase Inducer Phosphatase 2 (CDC25B). Then molecular docking using Autodock 4.6.2 was used in ligand and protein interaction simulation. Those 6 proteins were selected as macromolecules in the docking study.

Based on the docking result, we found that rosmarinic acid can bind MMP-1, MMP2, MMP-9, and MMP-12 active sites. The binding profile of rosmarinic acid with aldose reductase has similarities with other confirmed inhibitors. Docking with CDC25B showed that rosmarinic acid also binds in the same place as cyclin-dependent kinases (CDKs).

The ability of rosmarinic acid to inhibit MMP-1, MMP-2, MMP-9, aldose reductase, and CDC25B activity may underlie how rosmarinic acid is able to inhibit the development of breast cancer.

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