- The structural and chemical diversity of natural compounds represents a vast amount of potential in terms of new drug discovery. This project examines the cytotoxic potential of the marine natural product mandelalide A and seeks to understand whether or not exposure to this compound induces programmed cell death in cancer cells grown in culture. Human HeLa cervical cancer cells were examined for changes in morphology as well as expression of caspase-3 and poly(ADP-ribose) polymerase (PARP1), classic biomarkers of cell death signaling by apoptosis, when exposed to mandelalide A. It was found that mandelalide A caused time and concentration-dependent changes in HeLa cell morphology; cells treated with mandelalide A appeared rounded and eventually detached from the cell culture plates whereas vehicle-treated cells showed normal morphology and growth characteristics. Western blot analysis of HeLa cell lysates, grown in the presence and absence of mandelalide A, revealed cleaved forms of caspase-3 and PARP1 in mandelalide A treated cells, indicating apoptosis has occurred. Taken together these findings provide the first evidence that mandelalide A can induce time and concentration-dependent changes in HeLa cells that are consistent with apoptotic cell death.
Key Words: natural products, cell death, apoptosis, mandelalide A