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

Abstract

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.

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

“…Tumor angiogenesis can promote tumor cells to invade the blood system, thereby triggering tumor metastasis, which is one of the main obstacles to NSCLC treatment ( 34 ). Our results showed that 6h could suppress the production of MMPs (MMP-2 and MMP-9), thereby inhibiting the migration and invasion of NSCLC cells ( 35 ). Furthermore, the in vivo experiments proved that the tumor growth of nude mice was effectively inhibited after 6h treatment, and 6h did not cause detectable pathological abnormality of main organs.…”

Rosa hybrida Petal Extract Exhibits Antitumor Effects by Abrogating Tumor Progression and Angiogenesis in Bladder Cancer Both In Vivo and In Vitro

“…Common patterns of MIBC involve the proliferation, migration, and invasion of bladder cancer cells. 5 - 7 During neoplastic propagation, cancer cells tend to proliferate and metastasize via the multiple steps of biological processes, including the control of signaling pathways and cell cycle. 5 - 7 Uncontrolled tumor cell proliferation is involved in the phosphorylation of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/serine-threonine kinase (PI3K/AKT) signaling.…”

“… 5 - 7 During neoplastic propagation, cancer cells tend to proliferate and metastasize via the multiple steps of biological processes, including the control of signaling pathways and cell cycle. 5 - 7 Uncontrolled tumor cell proliferation is involved in the phosphorylation of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/serine-threonine kinase (PI3K/AKT) signaling. 6 - 9 In addition, advanced type of tumor cells are significantly associated with dysregulated cell cycle control because of the changes in cell cycle regulators, such as cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs), during the G 1 - to S-phase transition.…”

“… 5 - 7 Uncontrolled tumor cell proliferation is involved in the phosphorylation of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/serine-threonine kinase (PI3K/AKT) signaling. 6 - 9 In addition, advanced type of tumor cells are significantly associated with dysregulated cell cycle control because of the changes in cell cycle regulators, such as cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs), during the G 1 - to S-phase transition. 6 - 8 , 10 Matrix metalloproteinases (MMPs), especially MMP-9, participate in migration and invasion of cancer cells during the advanced stage of bladder cancer.…”

“… 11 - 14 Several transcription factors, such as the nuclear factor-kappa-B (NF-κB), Sp-1, and AP-1, were observed to enhance the expression levels of MMP-9 in bladder cancer cells. 6 , 7 , 15 , 16…”