Exploring the Anticancer Potential of Launaea mucronata: Biological Assessment, Molecular Docking, and Molecular Dynamics Simulations.

BACKGROUND Launaea mucronata has garnered the interest of chemists, particularly in the field of oncology. While not traditionally used for cancer treatment, studies have shown that its methanolic extract exhibits cytotoxic effects against human cancer cell lines.

METHODS Herein, thirty-three metabolites were spotted in the aqueous extract of Launaea mucronata via UPLC-MS/MS, primarily flavonoids, hydroxycinnamic acid derivatives, and carboxylic acid derivatives. The extract's antiproliferative activity was tested on HCT-116 (colon), MCF7 (breast), and HePG2 (liver) cancer cells, showing notable potency. A molecular docking study assessed the extract's bioactive compounds for their binding to human DNA-Topo II enzyme complexes. Molecular dynamics simulations (200 ns) were performed on the top-scoring complexes (dicaffeoyl-succinoylquinic acid 7, tricaffeoyl quinic acid 10, feruloyl-O-p-coumaroyl- O-caffeoylshikimic acid 12, and kaempferol-rutinoside 23) using Schrödinger's Desmond package. Binding stability was further validated by MM-GBSA energy calculations via Schrödinger's thermal_mmgbsa.py script.

RESULTS The IC50 values were 5.35 ± 0.09 μg/mL in the HePG2 cell line versus 48.99 ± 21.51 μg/mL for doxorubicin. Similarly, for the MCF7 cells, the recorded IC50 of the extract was found to be 5.60 ± 1.15 μg/mL versus 4.97 ± 0.35 μg/mL for doxorubicin.

DISCUSSION A total of 33 metabolites of Launaea mucronata identified via UPLC-MS/MS were identified as promising anticancer candidates against both HePG2 and MCF7 cell lines. Additionally, their mechanisms of action involve DNA intercalation and inhibition of topoisomerase II (Topo II) through molecular docking, molecular dynamics, and MM-GBSA calculations.

CONCLUSION These findings highlight Launaea mucronata's promising anticancer potential, supported by both experimental and computational evidence.