Malformin A1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through stimulation of the p38 signaling pathway

Malformin A1 (MA1), a cyclic pentapeptide isolated from Aspergillus niger, has been found to possess a range of bioactive properties including Antibacterial activity. However, it is unclear whether MA1 exerts an Anticancer effect or not. In this study, we conducted in vitro experiments to investigate its Anticancer properties in human colorectal Cancer cells. The effect of MA1 on human colorectal Cancer cells, SW480 and DKO1, was examined by the WST-1 cell viability assay, inverted microscopy, 5-bromo-2-deoxyuridine (BrdU) incorporation, flow cytometry, DNA fragmentation, wound healing, Transwell assays, and western blotting. MA1 treatment showed potent cytotoxic activities on human colorectal Cancer cells. MA1 treatment induced Apoptosis by activating the poly(ADP-ribose) polymerase (PARP), caspase‑3, -7, and -9. MA1 treatment led to the increase in p53 upregulated modulator of Apoptosis (PUMA) and the decrease in X-linked inhibitor of Apoptosis protein (XIAP) and Survivin. In addition, MA1 treatment induced cell cycle arrest in the sub-G1 phase. The pan-caspase inhibitor, Z‑VAD‑FMK, attenuated these MA1-induced apoptotic effects on human colorectal Cancer cells. Moreover, MA1 treatment suppressed tumor cell migration and invasion. The phosphorylation level of p38 was upregulated by MA1 treatment, and the inhibitor of p38, SB203580, attenuated the MA1-induced p38 phosphorylation as well as caspase‑3 and PARP activation. These results indicate that MA1 treatment alters invasive and oncogenic phenotypes of human colorectal Cancer cells through the stimulation of the p38 signaling pathway.