N-methylsansalvamide elicits antitumor effects in colon cancer cells in vitro and in vivo by regulating proliferation, apoptosis, and metastatic capacity
Open Access
- 16 March 2023
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 14, 1146966
- https://doi.org/10.3389/fphar.2023.1146966
Abstract
N-methylsansalvamide (MSSV), a cyclic pentadepsipeptide, was obtained from a strain of Fusarium solani f. radicicola. The current study investigated the anti-colorectal cancer effect of MSSV. MSSV exhibited the inhibition of the proliferation in HCT116 cells via induction of G0/G1 cell cycle arrest by downregulating CDK 2, CDK6, cyclin D, and cyclin E, and upregulating p21WAF1 and p27KIP1. Decreased phosphorylation of AKT was observed in MSSV-treated cells. Moreover, MSSV treatment induced caspase-mediated apoptosis through elevating the level of cleaved caspase 3, cleaved PARP, cleaved caspase 9, and pro-apoptotic Bax. MSSV revealed the declined MMP-9 level mediated by reduction in the binding activity of AP-1, Sp-1, and NF-κB motifs, which led to the migration and invasion of HCT116 cells. In vitro metabolism with rat liver S9 fractions was performed to examine the effect of MSSV metabolites. The metabolic process enhanced the inhibitory effect of MSSV on the HCT116 cell proliferation via decline of cyclin D1 expression and AKT phosphorylation. Finally, oral administration of MSSV inhibited the tumor growth of HCT116 xenograft mice. These results suggest that MSSV is a potential anti-tumor agent in colorectal cancer treatment.Funding Information
- Chung-Ang University (2021년 중앙대𝕙교 연구비 지원)
- National Research Foundation of Korea (교육부 [2018R1A6A1A03025159])
This publication has 46 references indexed in Scilit:
- In vitro cell migration and invasion assaysMutation Research - Reviews in Mutation Research, 2013
- Cancer Treatment Using Peptides: Current Therapies and Future ProspectsJournal of Amino Acids, 2012
- Analgesic‐antitumor peptide inhibits proliferation and migration of SHG‐44 human malignant glioma cellsJournal of Cellular Biochemistry, 2011
- Matrix Metalloproteinases: Regulators of the Tumor MicroenvironmentCell, 2010
- Desmethoxymajusculamide C, a Cyanobacterial Depsipeptide with Potent Cytotoxicity in Both Cyclic and Ring-Opened FormsJournal of Natural Products, 2009
- Signal transduction by focal adhesion kinase in cancerCancer and Metastasis Reviews, 2009
- AKT/PKB Signaling: Navigating DownstreamCell, 2007
- Surfactin from Bacillus subtilis displays anti‐proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppressionFEBS Letters, 2007
- Signal Transduction from the Extracellular Matrix. A Role for the Focal Adhesion Protein-tyrosine Kinase FAK.Cell Structure and Function, 1996
- Detoxification pathways in the liverJournal of Inherited Metabolic Disease, 1991