A Novel Cyclic Pentadepsipeptide, N -Methylsansalvamide, Suppresses Angiogenic Responses and Exhibits Antitumor Efficacy against Bladder Cancer

Here, we explored the anti-tumor efficacy of a cyclic pentadepsipeptide, -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-a...

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Bibliographic Details
Published in:Cancers 2021-01, Vol.13 (2), p.191
Main Authors: Song, Jun-Hui, Park, Juhee, Park, Sung Lyea, Hwang, Byungdoo, Kim, Wun-Jae, Lee, Chan, Moon, Sung-Kwon
Format: Article
Language:English
Subjects:
Acute toxicity
AKT protein
Amino acids
Angiogenesis
Antitumor activity
Apoptosis
Bladder cancer
Cancer
Cancer therapies
Cell cycle
Cell proliferation
Cytotoxicity
Gelatinase B
Invasiveness
Kinases
Matrix metalloproteinase
Metalloproteinase
Metastasis
Molecular structure
Oral administration
Peptides
Polyclonal antibodies
Proteins
Vascular endothelial growth factor
Xenografts
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Summary:Here, we explored the anti-tumor efficacy of a cyclic pentadepsipeptide, -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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13020191