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[Corrigendum] 3‑Bromopyruvate sensitizes human breast cancer cells to TRAIL‑induced apoptosis via the phosphorylated AMPK‑mediated upregulation of DR5
- Source :
- Oncology Reports
- Publication Year :
- 2022
- Publisher :
- Spandidos Publications, 2022.
-
Abstract
- Previous studies have indicated that the sensitivity of breast cancer cells to tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced apoptosis is associated with the expression of death receptors on the cell membrane. However, drug resistance limits the use of TRAIL in cancer therapy. Numerous studies have indicated that death receptors, which induce apoptosis, are upregulated by the endoplasmic reticulum (ER) stress response. 3‑Bromopyruvate (3‑BP), an anticancer agent, inhibits cell growth and induces apoptosis through interfering with glycolysis. In the present study, it was demonstrated that 3‑BP synergistically sensitized breast cancer cells to TRAIL‑induced apoptosis via the upregulation of death receptor 5 (DR5). Furthermore, we found that the protein levels of glucose‑related protein 78 (GRP78) and CCAAT‑enhancer‑binding protein homologous protein (CHOP) increased following treatment with 3‑BP. The expression of Bax (in MCF‑7 cells) and caspase‑3 (in MDA‑MB‑231 cells) increased following co‑treatment with 3‑BP and TRAIL, whereas the expression of the anti‑apoptotic protein Bcl‑2 decreased. In order to investigate the molecular mechanism regulating this effect, the expression of adenosine monophosphate‑activated protein kinase (AMPK), activated by 3‑BP, was determined. It was demonstrated that phosphorylated‑AMPK was upregulated following treatment with 3‑BP. Notably, Compound C, an AMPK inhibitor, reversed the effects of 3‑BP. Finally, a synergistic antitumor effect of 3‑BP and TRAIL was observed in MCF‑7 cell xenografts in nude mice. In conclusion, these results indicated that 3‑BP sensitized breast cancer cells to TRAIL via the AMPK‑mediated upregulation of DR5.
- Subjects :
- 0301 basic medicine
Cancer Research
Mice, Nude
Antineoplastic Agents
Apoptosis
Breast Neoplasms
AMP-Activated Protein Kinases
TNF-Related Apoptosis-Inducing Ligand
03 medical and health sciences
Mice
Downregulation and upregulation
Animals
Humans
Phosphorylation
Protein kinase A
Pyruvates
Endoplasmic Reticulum Chaperone BiP
Cell Proliferation
Mice, Inbred BALB C
Cell growth
Chemistry
AMPK
Drug Synergism
General Medicine
Cell cycle
Endoplasmic Reticulum Stress
Xenograft Model Antitumor Assays
Recombinant Proteins
Up-Regulation
Receptors, TNF-Related Apoptosis-Inducing Ligand
030104 developmental biology
Pyrimidines
Oncology
Drug Resistance, Neoplasm
Cancer cell
Cancer research
MCF-7 Cells
Pyrazoles
Tumor necrosis factor alpha
Female
Corrigendum
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....42a1acbe456a120bf3f0908e10036e5c
- Full Text :
- https://doi.org/10.3892/or.2022.8264