Triple-negative breast cancer(TNBC)represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options.This investigation examined the anticancer potential of Caerulomycin A(Cae A...Triple-negative breast cancer(TNBC)represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options.This investigation examined the anticancer potential of Caerulomycin A(Cae A),a natural compound derived from marine actinomycetes,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 induction.Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum(ER)stress and subsequent upregulation of C/EBP homologous protein(CHOP)expression,resulting in mitochondrial damage-mediated apoptosis.Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis,highlighting the essential 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 diminished energy metabolism potentially triggers ER stress and subsequent apoptosis.Furthermore,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.展开更多
The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluo...The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluorescence image in Figure 4G”.展开更多
基金supported by the Science and Education Integration Project by the Innovation and Entrepreneurship Office of Nanjing University(No.0214-1480608207)Jiangsu Provincial Research Hospital(No.YJXYY202204)。
文摘Triple-negative breast cancer(TNBC)represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options.This investigation examined the anticancer potential of Caerulomycin A(Cae A),a natural compound derived from marine actinomycetes,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 induction.Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum(ER)stress and subsequent upregulation of C/EBP homologous protein(CHOP)expression,resulting in mitochondrial damage-mediated apoptosis.Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis,highlighting the essential 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 diminished energy metabolism potentially triggers ER stress and subsequent apoptosis.Furthermore,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.
文摘The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluorescence image in Figure 4G”.
