Cleome spinosa Jacq. Extract Induces Apoptosis in Ehrlich ascites Carcinoma Cells by Regulating p53 and Bcl-xL
摘要
Cleome is the largest genus of the family Cleomaceae, which is known for remedial applications in a range of diseases. Several species of Cleome genus have been shown to have anti-cancer properties; however, very little has been reported on the species spinosa. The present study has examined the potential anti-cancer property of ethanolic leaf extract of Cleome spinosa Jacq. (CSE) in Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo. Morphological changes, reminiscent of apoptosis, in CSE-treated EAC cells were examined via brightfield, fluorescence, and electron microscopies. The protein levels of p53 and Bcl-xL were measured using western blot. Gas chromatography and mass spectrometry (GC–MS) were carried out to identify the bioactive compounds present in CSE, followed by in silico modeling. CSE-induced death in EAC cells was similar to bleomycin. Microscopic studies revealed apoptotic changes in CSE-treated EAC cells such as surface blebbing, nuclear fragmentation, chromatin condensation, and apoptotic body formation. This coincided with upregulation of pro-apoptotic protein, p53, and downregulation of anti-apoptotic protein, Bcl-xL in vitro, as well as in vivo. GC–MS analysis identified 43 phytocompounds in the CSE. In silico molecular docking analysis indicated that cycloartenol, stigmasterol, clionasterol, beta-sitosterol, lupenone, and sitostenone, had strong binding affinities for p53 and Bcl-xL. Thus, CSE-derived compounds appear to induce apoptosis through upregulation of p53 and downregulation of Bcl-xL proteins in the EAC model and can be considered a promising natural compound for future cancer therapies.
Graphical abstract