Betulin: a novel triterpenoid anti-cancerous agent targeting cervical cancer through epigenetic proteins

Area of Science:

• Oncology
• Bioinformatics
• Pharmacology

Background:

• Cervical cancer (CCa) remains a significant global health concern for women.
• Conventional treatments for CCa are often costly and associated with severe side effects, necessitating the exploration of novel therapeutic agents.
• Epigenetic modifications play a crucial role in CCa development, making epigenetic targets like DNMT3A, HDAC4, and KMT2C promising avenues for drug discovery.

Purpose of the Study:

• To investigate the potential of triterpenoids as anti-cancer agents against cervical cancer by targeting epigenetic proteins DNMT3A, HDAC4, and KMT2C.
• To identify a lead compound with favorable anti-cancer efficacy and drug-like properties using a bioinformatic approach.
• To evaluate the molecular interactions, stability, and in vitro efficacy of the identified lead compound.

Main Methods:

• Bioinformatic analysis including molecular docking, ADMET prediction, and Molecular Dynamics (MD) simulations.
• Density Functional Theory (DFT) calculations to assess molecular activity and stability.
• In vitro evaluation using MTT assay to determine the IC50 value of the lead compound.

Main Results:

• Betulin (BE) was identified as a potential lead compound with strong binding affinities to DNMT3A, HDAC4, and KMT2C, outperforming standard drugs in docking scores.
• MD simulations confirmed the structural stability and compactness of the BE-protein complexes.
• DFT analysis indicated high molecular activity and kinetic stability for BE.
• In vitro MTT assay demonstrated significant anti-cancer activity with an IC50 of 15 µg/ml for BE against CCa cells.

Conclusions:

• Betulin (BE) exhibits significant potential as a novel therapeutic agent for cervical cancer due to its potent inhibition of key epigenetic targets and favorable pharmacokinetic and toxicity profiles.
• The findings suggest that BE warrants further investigation in in vivo models to fully elucidate its therapeutic potential for cervical cancer treatment.