The effects of the
flavonoid compound,
kaempferol, which is an inhibitor of
cancer cell proliferation and an inducer of cell apoptosis have been shown in various
cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in
bladder cancer. Here, we investigated the effects of
kaempferol on
bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various
bladder cancer cell lines showed that
kaempferol enhanced
bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis,
DNA ladder experiment, and TUNEL assay,
kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with
kaempferol significant suppression in
tumor growth compared to the control group mice.
Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the
kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed
kaempferol can also inhibit
bladder cancer invasion and
metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the
kaempferol mediated cell proliferation inhibition. All these findings suggest
kaempferol might be an effective and novel chemotherapeutic
drug to apply for the future therapeutic agent to combat
bladder cancer.