Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells

• Published in: Biomolecules & therapeutics Vol. 32; no. 1; pp. 123 - 135
• Main Authors: Lee, Jee-Hyung, Choi, Jin Ho, Lee, Kyung-Min, Lee, Min Woo, Ku, Ja-Lok, Oh, Dong-Chan, Shin, Yern-Hyerk, Kim, Dae Hyun, Cho, In Rae, Paik, Woo Hyun, Ryu, Ji Kon, Kim, Yong-Tae, Lee, Sang Hyub, Lee, Sang Kook
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.01.2024
• Subjects: Original; Patient-derived pancreatic cancer organoids (PDPCOs); Piceamycin; Alpha-actinin-4 (ACTN4); Pancreatic cancer; Apoptosis
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2023.109

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of , a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G /G phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.