Caerulomycin A disrupts glucose metabolism and triggers ER stress-induced apoptosis in triple-negative breast cancer cells.
10.1016/S1875-5364(25)60919-8
- Author:
Ye ZHANG
1
;
Shanshan SU
1
;
Xiaoyu XU
1
;
Zhixian HE
2
;
Yiyan ZHOU
2
;
Xiangrong LU
3
;
Aiqin JIANG
4
Author Information
1. Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
2. Affiliated Hospital of Nantong University, Nantong 226001, China.
3. Nanjing University School of Life Sciences, Nanjing 210023, China. Electronic address: 231505022@smail.nju.edu.cn.
4. Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China. Electronic address: jianaq@nju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
CHOP;
Caerulomycin A;
Glucose metabolism;
Triple negative breast cancer
- MeSH:
Humans;
Endoplasmic Reticulum Stress/drug effects*;
Triple Negative Breast Neoplasms/genetics*;
Apoptosis/drug effects*;
Cell Line, Tumor;
Female;
Animals;
Glucose/metabolism*;
Mice;
Cell Proliferation/drug effects*;
Transcription Factor CHOP/genetics*;
Antineoplastic Agents/pharmacology*;
Mitochondria/metabolism*;
Mice, Inbred BALB C
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1080-1091
- CountryChina
- Language:English
-
Abstract:
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 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.
