Bioactivity-guided isolation of anti-proliferative compounds from <i>Curcuma zedoaria</i> against triple negative breast cancer cells

Triple-negative breast cancer (TNBC) presents limited clinically effective treatment options. <i>Curcuma zedoaria</i> (<i>C. zedoaria</i>), a traditional medicine, has been used in China to treat various cancers including TNBC, although its active components remain unclear. Herein, we applied multidimensional liquid chromatography combined with bioactivity assay to discover anti-proliferative compounds against TNBC cells from <i>C. zedoaria</i>. Initially, 26 fractions were generated through first-dimensional reverse-phase liquid chromatography and profiled using SUM159 cells for its anti-proliferative activity. Two active fractions were identified and separated. Following the third-dimensional separation, we successfully isolated two compounds, diarylheptanoid a and diarylheptanoid b, and found that both compounds displayed moderate potency in inhibiting SUM159 proliferation with IC₅₀ values of 19.82 ± 3.08 μM and 28.16 ± 1.97 μM, respectively. Transcriptome analysis revealed that the differentially expressed genes induced by diarylheptanoid a were mainly concentrated with the actin function and involved in motor protein pathways. This study suggests that diarylheptanoids may contribute to the anti-TNBC effects of <i>C. zedoaria</i> and provide potential scaffolds for anti-TNBC drug development.