Investigating the combined effects of jadomycin B and celecoxib against triple-negative breast cancer using zebrafish larval xenografts

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, shown to be enhanced when combined with selective COX-2 inhibitor, celecoxib (CXB). Our objectives were to generate a fluorescent human TNBC cell line, as well as evaluate the toxicity and anticancer effect of JB combined with CXB using zebrafish larval xenografts. 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 was determined for JB (20 mM) and CXB (5 mM). Zebrafish embryos were xenotransplanted with 231-EGFP cells and treated with the MTD of JB CXB. 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 the safety and efficacy of JB combined with CXB in a zebrafish larval xenograft model for human TNBC, enhancing anticancer effects, similar to effects previously determined in vitro.