Evaluation of milk thistle (Silybum marianum) phytochemicals as curative agents of retinoblastoma using in-silico approach

Introduction

Retinoblastoma is a malignant tumour that primarily affects children under the age of five. This cancer arises from retinoblasts, leading to a distinctive symptom known as leukocoria, which is a white reflection visible when light shines on the retina. Retinal cells proliferate uncontrollably as a result of mutations in the allele of the retinoblastoma gene (RB1) which indirectly cause overexpression of CDK4 and CDK6 proteins. Milk thistle has the ability to inhibit cancer cell growth, prevent angiogenesis, halt metastasis, induce apoptosis, and enhance effectiveness of chemotherapy and radiation treatments.

Methods

In this study, ligands were retrieved to investigate potential of milk thistle in treating retinoblastoma and it’s in silico interaction with CDK4, CDK6, and pRb proteins were assessed through molecular docking techniques. The drug-likeness of all ligands was assessed by Lipinski rule of five. The PyMOL program was used to convert PDB format of the CDK4, CDK6, and pRb receptors into PDBQT format, and to identify active sites on the proteins. The drug-ability, lead likeness, pharmacokinetics, and physicochemical properties of ligands were assessed using SwissADME.

Results

The drug-likeness of all ligands followed Lipinski's rule with no violations of any of the five parameters. The binding affinity of milk thistle ligands to CDK4, CDK6, and pRB proteins was found to be high ranging from −3 to −9.9 kcal/mol, suggesting the potential of milk thistle as a treatment for retinoblastoma. Milk thistle is a useful treatment option for cancer, because of its anti-proliferative, anti-angiogenisis, anti- metastasis and induce apoptosis properties. ADMET analysis provided insights into the oral bioavailability, pharmacokinetics, water solubility, and physicochemical properties of the ligands.

Conclusions

The findings indicated that phytochemicals derived from milk thistle hold promising potential as a therapeutic option for retinoblastoma due to its diverse mechanisms of action, positive safety profile, and prospective synergistic effects with conventional therapies.