Can J Physiol Pharmacol. 2025 Nov 12. doi: 10.1139/cjpp-2025-0117. Online ahead of print.
ABSTRACT
Breast cancer affects 1 in 8 Canadian women over their lifetime. Triple-negative breast cancer (TNBC) represents 10-20% of all advanced stage breast cancers, often developing multi-drug resistance (MDR), commonly resulting in treatment failure. Jadomycin B (JB), a natural product of Streptomyces venezuelae, maintains cytotoxicity against MDR TNBCs, and its activity is enhanced when combined with selective COX-2 inhibitor, celecoxib (CXB) in vitro. Our objectives were to evaluate the toxicity and anticancer effects of JB combined with CXB using zebrafish larval xenografts as a model system. Fluorescent human TNBC MDA-MB-231 cells (231-EGFP) were generated and characterized for zebrafish larval xenografts. A maximum tolerated dose (MTD) in zebrafish larvae were determined for JB (20 mM) and CXB (5 mM). Zebrafish embryos were xenotransplanted with 50 to 100 231-EGFP cells and treated with the MTDs of JB and CXB alone or in combination. The combination of JB and CXB resulted in a 75% reduction in 231-EGFP fluorescence intensity, significantly higher than reductions caused by either drug alone (39% for JB, 15 % for CXB) (p <0.05). This study demonstrates that combining JB with CXB enhances anticancer activity in a zebrafish larval xenograft model of human TNBC, validating effects previously determined in vitro.
PMID:41223403 | DOI:10.1139/cjpp-2025-0117
