Anticancer Activity of Cardiac Glycosides from Acokanthera Species withEmphasis on Their Mechanism of Action

Abstract

Cancer is a disease the cause a wide and huge mortality ratio all over the world especially lung cancer of NSCLC type. Because of the severe side effects of traditional chemotherapy and its severe side effects, the attention now is directed towards identification of anticancer activity of natural products such as cardiac glycosides. In this study, the major cardiac glycosides in Acokantheraoppostifolia plant were isolated and then tested for several investigations of anticancer activity on A549 cells and also evaluated for effects induced when these cardiac glycosides were combined with the traditional chemotherapeutic agents used as treatment for (NSCLC) Non-small cell lung cancer. The plant was extracted by 95% ethanol then fractionation and isolation resulted in 500mg of white needle crystals of cardiac glycosides which were identified through NMR spectroscopy that indicate to a major cardiac glycoside called Acovenoside A. several anticancer investigation were done for the isolated cardiac glycosides and the traditional chemotherapy and for combinations of them as viability and cytotoxicity assays. Investigations on cardiac glycosides indicated to IC50 of 395.901ug/ml while IC50 of taxol and carboplatin were 66.07ug/ml and 230.18ug/ml respectively with significant reduction in cell viability. Same investigations were done for different combination protocola as taxol and carboplatin that result in reduction in cell viability to 87.5%, 85.38%, 95.4% and 95.67%. While other combinations that include cardiac glycoside with taxol result in reduction in cell viability to 32.3% but with carboplatin results in 49.15% cell viability. The triple combination that include the three drugs results in 21.09% cell viability which indicate to the value of adding cardiac glycoside to the regimen. Flowcytometic analysis was done by Annexin V-FITC Assay Protocol that proved that cardiac glycoside in combinations induce preG apoptosis and cell growth arrest in different cell cycle phases depending on the composition of the combination.