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

• Published in: Journal of natural products (Washington, D.C.) Vol. 85; no. 12; pp. 2817 - 2827
• Main Authors: Kyaw, Kay Zin, Byun, Woong Sub, Shin, Yern-Hyerk, Huynh, Thanh-Hau, Lee, Ji Yun, Bae, Eun Seo, Park, Hyen Joo, Oh, Dong-Chan, Lee, Sang Kook
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 23.12.2022
• Subjects: Animals; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Lactams, Macrocyclic; Mice; Up-Regulation
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.2c00832

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.