Bladder cancer is one of the most frequent
cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress
cancer progression) to induce targeted apoptosis for
cancer therapy.
Capsaicin, which has anti-
cancer properties, is one such agent. It is known to preferentially inhibit a
tumor-associated NADH oxidase (tNOX) that is preferentially expressed in
cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of
capsaicin in human
bladder cancer cells. We showed that
capsaicin downregulates tNOX expression and decreases
bladder cancer cell growth by enhancing apoptosis. Moreover,
capsaicin was found to reduce the expression levels of several
proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest.
Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of
paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of
sirtuin 1 (
SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that
capsaicin inhibits the growth of
bladder cancer cells by inhibiting tNOX and
SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.