Aim and Background: The methanolic extract of
Lepidium sativum L. was known for its
free radical scavenging potential and anticancer properties. The aim was to perform a
comparative investigation of the cytotoxic and cell death potential of the Soxhlet (SOX)
and crude methanolic extract (CRU). `Materials and Methods: MTT as well as the
PI-based assays in caspase-3-deficient, MCF-7 human breast cancer cells, for its cytotoxic
potential and synergistic effect. LC-QTOF-MS/MS was used for characterization. These
bioactive molecules were docked with human caspase-6 (2WDP) as well as its zymogen
variant (4IYR) to mimicking a more physiological form of cell demise. Results: Both
extracts showed a dose-dependent toxicity and the IC50 was found to be 136.75μg/ml,
and 88.49 μg/ml compared with that of standard quercetin (8.72μg/ml). At their IC50
concentrations, the corresponding PI-based flow cytometry and cell death values were
31.5±3% and 32.4±5.6, while that of quercetin was 36.9±7.4 %. A synergy in cell
death was seen for a combination of
L. sativum extracts (CRU-MeOH & SOX-MeOH)
and quercetin. Thirteen (13) compounds were reported for the first time in this seed by
LC-MS/MS. Good binding affinity was seen with both human caspase -6 (2WDP) and
the mutated zymogen (4IYR) with reference to that of quercetin. Conclusion: This
in vitro/
in silico correlation showed that the methanolic extracts of
L. sativum exhibited a
significantly higher level of cell death in MCF-7 cells. Also, their synergistic increases in
cell death provides a basis possibly for a combination therapy-based strategy.