Cytotoxicity of Cucurbitacin E Extracted from Ecballium elaterium and Anticancer Agents in Vitro

Objective: The objective of this present investigation was to determine the effects of Cucurbitacin E (CuE) extracted from Ecballium elaterium A.Rich., Fam. Cucurbitaceae, on three cancer cell lines (breast, prostate and melanoma) and a normal transformed cell line (fibroblasts), compared to other cytotoxic agents. Methods: Cytotoxicity was assessed by an array of assays including total and viable count determinations, lactate dehydrogenase enzyme release, morphological changes, effects on mitochondrial metabolism, agarose gel electrophoresis for apoptotic changes, median inhibitory concentration determination and interaction studies. Results: CuE exhibited a marked effect on prostate adenocarcinoma cells at a median inhibitory concentration (IC₅₀) of 9.35 nM and moderate effects on melanoma and breast carcinoma cells (IC50 = 0.87 and 1.95 µM, respectively). Parameters that showed a reduction in cell viability were prominent with the compound, as compared to the controls. Morphologically, the cancer cells exhibited nuclear and cytoplasmic (N/C) changes such as condensation of chromatin, an increase in the N/C ratio, and rounding up of the cytoplasm. Surface blebbing and morphological signs of apoptosis occurred in all cancer cell types. In the agarose-gel electrophoresis analysis, DNA ladder characteristic of apoptosis, was exhibited by the CuE treatment on both prostate and breast cancer cell lines, as for tamoxifen and mesterolone, respectively. Negligible cytotoxic effects were observed on normal fibroblasts as compared to the control. Conclusion: Owing to its chemical structure, CuE can be used as a lead drug in the development of cytotoxic agents with low toxicity on normal cells.