Here, we explored the anti-
tumor efficacy of a cyclic pentadepsipeptide,
N-methylsansalvamide (MSSV), in
bladder cancer. MSSV inhibited the proliferation of both
bladder cancer 5637 and T24 cells, which was attributed to the G1-phase cell cycle arrest, apoptosis induction, and alteration of
mitogen-activated protein kinases (MAPKs) and
protein kinase b (AKT) signaling pathways. Additionally, the treatment of
bladder cancer cells with MSSV suppressed migratory and invasive potential via the
transcription factor-mediated expression of
matrix metalloproteinase 9 (MMP-9). MSSV abrogated
vascular endothelial growth factor (
VEGF)-induced angiogenic responses in vitro and in vivo. Furthermore, our result showed the potent anti-
tumor efficacy of MSSV in a xenograft mouse model implanted with
bladder cancer 5637 cells. Finally, acute toxicity test data obtained from blood biochemical test and liver staining indicated that the
oral administration of MSSV at 2000 mg/kg caused no adverse cytotoxic effects. Our preclinical data described the potent anti-angiogenic and anti-
tumor efficacy of MSSV and showed no signs of acute toxicity, thereby suggesting the putative potential of oral MSSV as a novel anti-
tumor agent in
bladder cancer treatment.