New Hope for Breast Cancer Involving Triggering Necroptosis Using a Phytochemical from Eomecon Chionantha
Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 11, 2025 3 hours, 7 minutes ago
Medical News: Breast cancer, a devastating health challenge worldwide, affects millions each year, accounting for one in every eight cancer diagnoses globally. Despite advancements in treatments, including chemotherapy, radiotherapy, and hormonal therapy, resistance to these therapies remains a critical hurdle. Scientists are continually exploring alternative pathways to combat breast cancer effectively, and recent research into necroptosis offers a glimmer of hope. Necroptosis, a form of regulated cell death, differs significantly from apoptosis and could provide an innovative avenue for treating resistant breast cancers.
New Hope for Breast Cancer Involving Triggering Necroptosis Using a Phytochemical from
Eomecon Chionantha
The Focus on Necroptosis
Necroptosis has emerged as a promising target in cancer treatment due to its unique mechanisms of inducing cell death. Unlike apoptosis, which cancer cells often evade, necroptosis involves a cascade of events leading to cell membrane rupture and the release of cellular contents. This pathway involves three critical proteins: receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like protein (MLKL). By targeting these proteins, researchers aim to develop therapies that can overcome the resistance seen in traditional treatments.
Eomecon Chionantha and the Discovery of SG-A
In an exciting development, scientists have identified 8,12-dimethoxysanguinarine (SG-A), a compound extracted from the plant Eomecon chionantha. This
Medical News report delves into groundbreaking research led by teams from Jadara University, Aqaba University of Technology, Saveetha Institute of Medical and Technical Sciences, Quanta Calculus, MAHSA University, and Al al-bayt University.
These researchers explored SG-A’s potential to trigger necroptosis in MCF-7 breast cancer cells through advanced computational methods, including molecular docking, molecular dynamics, density functional theory (DFT), and molecular electrostatic potential (MEP) analyses.
Key Findings of the Study
-Molecular Docking Insights
The study revealed that SG-A exhibited a strong binding affinity to MLKL, with a binding energy of −9.40 kcal/mol, outperforming its interaction with RIPK1 (−6.37 kcal/mol) and RIPK3 (−7.01 kcal/mol). The higher affinity to MLKL suggests SG-A’s specificity and efficacy in targeting this critical protein in the necroptosis pathway.
-Stability and Dynamics
Through molecular dynamics simulations, SG-A demonstrated remarkable stability when bound to MLKL. Root Mean Square Deviation (RMSD) values stabilized between 1.4 and 3.3 Å over a 300-nanosecond simulation. Additionally, the compound maintained two hydrogen bonds with MLKL throughout the simulation period, enhancing the stability and reinforcing its potential as a necroptosis
inducer.
-Electrostatic and Binding Energy Analysis
The MM-PBSA analysis further substantiated SG-A’s efficacy, showing a binding free energy of −31.03 kcal/mol with MLKL, surpassing the control ligand’s binding energy of −23.96 kcal/mol. Key amino acid residues, particularly ARG149, contributed significantly to this binding stability, with a notable energy contribution of −176.24 kcal/mol.
DFT and MEP Studies
SG-A’s electronic properties, characterized by a narrow band gap and favorable molecular electrostatic potential, highlight its suitability for stable interactions with MLKL. The dipole moment and other quantum molecular descriptors indicate a compound that is highly reactive yet stable within biological environments, making it an ideal candidate for therapeutic development.
Implications of the Findings
This research not only highlights SG-A’s potential as a targeted therapy for breast cancer but also underscores the importance of exploring necroptosis as an alternative pathway for cancer treatment. The ability of SG-A to induce necroptosis selectively in breast cancer cells, particularly those resistant to apoptosis-inducing therapies, marks a significant step forward.
Study Conclusions
The comprehensive analyses conducted in this study indicate that SG-A, derived from Eomecon chionantha, holds substantial promise as a therapeutic agent against breast cancer. By effectively targeting MLKL and inducing necroptosis, SG-A could pave the way for novel treatments that address the limitations of current therapies. However, while the computational findings are promising, experimental validation through in vitro and in vivo studies is imperative to confirm its therapeutic efficacy and safety.
The findings of this research were published in the peer-reviewed journal: PLOS ONE.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0313094
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