Cytotoxic, apoptotic activities and chemical profiling of dimorphic forms of Egyptian halophyte Cakile maritima scop.

Cakile maritima ssp. aegyptiaca (Wild.) Nyman is growing with dimorphic leaf forms (entire or pinnatifid lamina) along the Mediterranean coast of Egypt. The cytotoxic activities of dried shoot systems of the two morphological forms were evaluated by testing and comparing the effects of ethanolic and aqueous extracts on the viability of five human cell lines. GC-MS analysis was performed to identify the bioactive and anticancer compounds present in the most active extracts. MTT assay indicated that both aqueous and ethanolic extracts have selective cytotoxic activities against cancer cell lines with no inhibitory activities against normal Wi38 or Vero cell lines. The underlying mechanism of cytotoxicity involved the induction of G2/M phase arrest in targeted cells MCF-7 and HCT-116 associated with inducing apoptosis in both cell lines, as indicated by Annexin-V assay. Apoptosis investigation in MCF-7 and HCT-116 cells treated with ethanolic extracts, was further investigated through RT-PCR, which exhibited elevation of proapoptotic genes of P53, BAX, Capase-3,6,7,8,9, and downregulation of antiapoptotic gene (BCL-2) upon treatment. The GC-MS analysis of ethanolic extracts of pinnatifid and entire forms revealed the existence of 18 and 13 compounds, respectively, with eleven compounds that were detected in pinnatifid form only and seven compounds were identified exclusively in the entire form. Molecular Docking study revealed that the identified compounds exhibited good binding affinity towards BCL-2 inhibition, and this agreed with the suggested apoptotic mechanism. To the best of authors' knowledge, this is the first scientific evidence underline the variability in the chemical composition associated with variable anticancer activities of dimorphic forms of C. maritima.Communicated by Ramaswamy H. Sarma.