Several natural compound interfere with microtubules or the actin cytoskeleton. Compounds interfering with the microtubules like
Vinca-alkaloids or
taxanes, are extensively used for
cancer therapy. In contrast, knowledge about pharmacological properties of actin binding drugs is poor and drugs interfering with actin are far from clinical use.
Rhizopodin is a natural compound that strongly affects the actin cytoskeleton at nanomolar concentrations. Initial work revealed interesting anti-bacterial and cytotoxic effects, but the cellular effects and pharmacological properties of
rhizopodin have not been characterized. We hypothesized that
rhizopodin might exert anti-
cancer activity. Therefore, the aim of this study was to characterize the cellular and pharmacological effects of
rhizopodin in
cancer. Effects of
rhizopodin demonstrated prominent effects on the actin cytoskeleton as shown in the actin-
pyrene assay and by immunostaining of
cancer cells. To investigate cellular effects of
rhizopodin, we analyzed cell proliferation, cell death induction by
propidium iodide exclusion and western blot, as well as migration by impedance measurement using the xCELLligence device in MDA-MB-231
breast cancer and T24
bladder cancer cell lines.
Rhizopodin inhibited proliferation and induced cell death of MDA-MB-231 and T24 cells at nanomolar concentrations. PARP cleavage by
rhizopodin suggests
caspase-dependent cell death induction. Importantly,
rhizopodin potently inhibited MDA-MB-231 and T24
cancer cell migration at subtoxic doses where no actin aggregation was observed, indicating a specific underlying signaling of
rhizopodin. In summary, our study elucidates
rhizopodin as actin-binding natural compound that exerts potent anti-
cancer effects. Therefore, our work provides the basis for further in depth characterization of
rhizopodin as an antitumoral agent.