The
stilbene derivative,
cis-3,4',5-trimethoxy-3'-aminostilbene (
stilbene 5c), is a potentially potent
antitumor agent that acts via binding to the
colchicine-binding site in
tubulin. The current studies were designed to investigate the effectiveness of
stilbene 5c against the HCT-116 human
colon cancer cell line and B16/F10
melanoma cells as well as human endothelial cell tube formation and
tumor perfusion.
Stilbene 5c produced a time-dependent decrease in cell viability in both cell lines and the capacity of the cells to proliferate was not restored upon removal of the
drug. Treatment with
stilbene 5c also promoted both senescence and autophagy in both cell lines. TUNEL and
annexin 5 staining indicated that apoptosis also occurs in
stilbene 5c-treated HCT-116 cells, but not in B16/F10
melanoma cells.
DAPI staining revealed morphological changes in the cell nuclei (binucleated and micronucleated cells) indicative of mitotic catastrophe in HCT-116 cells but not in the B16/F10
melanoma cells. p53-null HCT-116 cells demonstrated a similar growth arrest/cell death response to
stilbene as p53-wild type HCT-116 cells.
Stilbene 5c also completely inhibited human endothelial cell tube formation on
Matrigel, consistent with potential anti-angiogenic actions. Using a new method developed for monitoring the pharmacodynamic effects of
stilbene 5c in vivo, we found that a single injection of
stilbene 5c reduced
tumor perfusion by 65% at 4h, returning to baseline by 24h, while subsequent daily
injections of
stilbene 5c produced progressively larger reductions and smaller rebounds. This work indicates that
stilbene 5c could potentially be effective against
melanoma and
colon cancer through the promotion of multiple modes of growth arrest and cell death coupled with anti-angiogenic and antivascular actions.