Tumour cell suppression by spiroleucettadine through dual regulation of cell cycle and apoptosis

Abstract

Background: Spiroleucettadine is an alkaloid originally derived from the yellow Leucetta sea sponge. Spiroleucettadine has previously been shown to inhibit the growth of various cancer cell lines and has a high anti-proliferative activity against a non-small cell lung cancer cell line (H522). The mediators of these anti-proliferative effects have not been determined. Therefore, in this study we measured changes in cell death and cell proliferation and their immediate protein mediators in response to spiroleucettadine, toward the aim of ultimately determining target(s) for spiroleucettadine in cancer cells and a more precise description of its mechanism of action. Methods: We used flow cytometry to investigate changes in the cell cycle apoptosis and Western blot to investigate associated protein changes following exposure of H522 cells to varying concentrations of spiroleucettadine. Results: We found evidence for cell cycle arrest at G2/M and associated increases in cyclin B1 expression and CDK1 phosphorylation, as well as an increase in apoptosis alongside marked increase in Bim expression, consistent with activation of the intrinsic apoptotic pathway Conclusions: Any targets for spiroleucettadine that may be proposed are constrained to those with mechanisms of actions that lead to G2/M arrest, induction of the intrinsic apoptotic pathway, and changes in the expression of associated proteins.