Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells
10.4062/biomolther.2023.109
- Author:
Jee-Hyung LEE
1
;
Jin Ho CHOI
;
Kyung-Min LEE
;
Min Woo LEE
;
Ja-Lok KU
;
Dong-Chan OH
;
Yern-Hyerk SHIN
;
Dae Hyun KIM
;
In Rae CHO
;
Woo Hyun PAIK
;
Ji Kon RYU
;
Yong-Tae KIM
;
Sang Hyub LEE
;
Sang Kook LEE
Author Information
1. Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, College of Medicine, Seoul Na- tional University, Seoul 03080, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2024;32(1):123-135
- CountryRepublic of Korea
- Language:EN
-
Abstract:
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 alpha-actinin-4, 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 G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited 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.
