Antiproliferative Effects of Nerium oleander Leaves and Their Cardiac Glycosides Odoroside A and Oleandrin on MCF-7 Cancer Cells

Background: Nerium oleander leaves extract preparations have been used for centuries against sores, abscesses and solid tumors. Objective: The aim of this study was to identify active compound(s) responsible for the antiproliferative activity of N. oleander leaves against MCF-7 breast cancer cell line and to explore their mechanisms of action. Methods: The methanolic extract and fractions were screened against four human cancer cell lines: HT-144, MCF-7, NCI-H460 and SF-268 using sulforhodamine B assay. The most active ethyl acetate soluble fraction led to the isolation of eleven pure compounds viz adynerigenin, adynerin, odoroside A, odoroside B, 5-O-kaempferobinoside, β-neriursate, oleanderocioic acid, oleandiginoside, oleandrin, 5-O-quercetibinoside and ursolic acid. The methanolic extract and the ethyl acetate soluble fraction exhibited significant growth inhibition (TGI: 0.14 to 3.3 μg/ml) against HT-144, MCF-7, NCI-H460 and SF-268 cell lines. The effects of the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin on the cytoskeleton and nuclei of MCF-7 cells were evaluated using immunofluorescence microscopy. Significant reduction in the mitotic index of MCF-7 cells were exhibited by the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin accompanied by morphological changes such as band-like arrangement of cells, reduction in F-actin processes, disruption of interphase microtubule network and condensation of nuclei. Results: These results support that the N. oleander leaves possess antiproliferative activity against the aforementioned cell lines particularly estrogen receptor positive MCF-7 cells, thereby justifying its traditional use against tumors. Moreover, the antiproliferative effects induced by the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin were possibly related to skeletal and nuclear morphological changes.