Antitumor Activity of Piceamycin by Upregulation of N-Myc Downstream-Regulated Gene 1 in Human Colorectal Cancer Cells

Abstract

Piceamycin (1), a macrocyclic lactam isolated from the silkworm's gut (Streptomyces sp. SD53 strain), reportedly possesses antibacterial activity. However, the potential anticancer activity and molecular processes underlying 1 have yet to be reported. Colorectal cancer (CRC) is high-risk cancer and accounts for 10% of all cancer cases worldwide. The high prevalence of resistance to radiation or chemotherapy means that patients with advanced CRC have a poor prognosis, with high recurrence and metastasis potential. Therefore, the present study investigated the antitumor effect and underlying mechanisms of 1 in CRC cells. The growth-inhibiting effect of 1 in CRC cells was correlated with the upregulation of a tumor suppressor, N-myc downstream-regulated gene 1 (NDRG1). Additionally, 1 induced G0/G1 cell cycle arrest and apoptosis and inhibited the migration of CRC cells. Notably, 1 disrupted the interaction between NDRG1 and c-Myc in CRC cells. In a mouse model with HCT116-implanted xenografts, the antitumor activity of 1 was confirmed by NDRG1 modulation. Overall, these findings show that 1 is a potential candidate for CRC treatment through regulation of NDGR1-mediated functionality.