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.

Potential Apoptotic Activities of Hylocereus undatus Peel and Pulp Extracts in MCF-7 and Caco-2 Cancer Cell Lines.

There is a huge demand for novel anticancer agents with fewer side effects compared to current therapies. Pitaya, or dragon fruit, is a reservoir of potent anticancer compounds. This research aimed to analyze the phytochemical components of Hylocereus undatus pulp and peel extracts using LC-MS and GC-MS, and to investigate the in vitro effects of both extracts against cancer (breast, MCF-7, and colon, Caco-2) and normal (lung; WI-38 and breast; MCF-10A) cell proliferation using the MTT assay. The apoptosis potential of the anticancer effects was also evaluated using flow cytometry, RT-PCR, and Western blot. The total phenolic and flavonoid contents in the peel extract were significantly higher than those in the pulp extract. Compared to the flavonoid and phenolic acid standards, the LC-MS analysis revealed the presence of nine compounds, which were represented as 84.32 and 5.29 µg/g of the flavonoids and 686.11 and 148.72 µg/g of the phenolic acids in the peel and pulp extracts, respectively. Among the identified compounds, chlorogenic acid, caffeic acid, ferulic acid, and rutin were found at the highest concentration in both plant extracts. Both extracts displayed cytotoxic activity against MCF-7 and Caco-2 cancer cells after 48 h of treatment at IC50 values ranging from 14 to 53 µg/mL with high selective indices against normal WI-38 and MCF-10A cell lines. The increase in apoptosis was revealed by the overexpression of p53, BAX, and caspase-9 and the downregulation of antiapoptotic Bcl-2 mRNA and protein expressions. The results indicate that H. undatus extracts can be a plant source for cancer therapy.

Nomad Jellyfish Rhopilema nomadica Venom Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Hepatocellular Carcinoma HepG2 Cells.

Jellyfish venom is a rich source of bioactive proteins and peptides with various biological activities including antioxidant, antimicrobial and antitumor effects. However, the anti-proliferative activity of the crude extract of Rhopilema nomadica jellyfish venom has not been examined yet. The present study aimed at the investigation of the in vitro effect of R. nomadica venom on liver cancer cells (HepG2), breast cancer cells (MDA-MB231), human normal fibroblast (HFB4), and human normal lung cells (WI-38) proliferation by using MTT assay. The apoptotic cell death in HepG2 cells was investigated using Annexin V-FITC/PI double staining-based flow cytometry analysis, western blot analysis, and DNA fragmentation assays. R. nomadica venom displayed significant dose-dependent cytotoxicity on HepG2 cells after 48 h of treatment with IC50 value of 50 µg/mL and higher toxicity (3:5-fold change) against MDA-MB231, HFB4, and WI-38 cells. R. nomadica venom showed a prominent increase of apoptosis as revealed by cell cycle arrest at G2/M phase, upregulation of p53, BAX, and caspase-3 proteins, and the down-regulation of anti-apoptotic Bcl-2 protein and DNA fragmentation. These findings suggest that R. nomadica venom induces apoptosis in hepatocellular carcinoma cells. To the best of the authors' knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest of R. nomadica jellyfish venom.