摘要Triple-negative breast cancer(TNBC)represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options.This investigation examined the anti-cancer potential of Caerulomycin A(Cae A),a natural compound derived from marine actino-mycetes,against TNBC.Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines,including 4T1,MDA-MB-231,and MDA-MB-468,through apoptosis induc-tion.Mechanistic analyses revealed that the compound induced sustained endoplasmic retic-ulum(ER)stress and subsequent upregulation of C/EBP homologous protein(CHOP)expres-sion,resulting in mitochondrial damage-mediated apoptosis.Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis,highlighting the essen-tial role of ER stress and CHOP in Cae A's anti-tumor mechanism.Both oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)decreased in TNBC cells following Cae A treatment,indicating reduced mitochondrial respiratory and glycolytic capacities.This dimin-ished energy metabolism potentially triggers ER stress and subsequent apoptosis.Further-more,Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity.The compound also effectively inhibited human TNBC organoid growth.These results indicate that Cae A may serve as a potential therapeutic agent for TNBC,with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.