Actinolactomycin from Streptomyces sp. CB00271: Isolation, Identification, and Potent Anti-Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited targeted therapies, underscoring an urgent need for novel agents. The soil-derived <i>Streptomyces</i> sp. CB00271, isolated from a biodiversity hotspot, was investigated for its bioactive metabolites. Bioassay-guided isolation led to the identification of actinolactomycin (<b>1</b>), alongside daidzein (<b>2</b>) and genistein (<b>3</b>). Remarkably, actinolactomycin (1) exhibited potent cytotoxicity against TNBC models, with IC₅₀ values of 0.72 ± 0.12 μM (MDA-MB-231) and 0.15 ± 0.02 μM (4T1), demonstrating approximately 9-fold and 31-fold greater potency than cisplatin, respectively, and suggesting action through targeted pathway inhibition. This study constitutes the first report to systematically highlight the exceptional anti-TNBC potential of this rare natural product, establishing it as a promising lead compound against this challenging subtype. Furthermore, <i>Streptomyces</i> sp. CB00271 is identified as a valuable and scarce microbial resource for actinolactomycin, providing a new avenue to address its supply limitation and facilitate future development.