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Inhibition of vacuolar H+ ATPase enhances sensitivity to tamoxifen via up-regulation of CHOP in breast cancer cells
- Source :
- Biochemical and Biophysical Research Communications. 437:463-468
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Resistance of estrogen receptor-positive breast cancer cells to tamoxifen represents a major barrier to the successful treatment of breast cancer. In the present study, we found that vacuolar H+ ATPase (vATPase) inhibitors, bafilomycin A1 and concanamycin A, sensitize tamoxifen-induced cell death. siRNA targeting ATP6V0C, a 16-kDa hydrophobic proteolipid subunit of vATPase that plays a central role in H+ transport, markedly increased cell death induced by tamoxifen. Interestingly, bafilomycin A1 induced up-regulation of DR4/DR5 and CHOP. Knock-down of CHOP by siRNA suppressed the cell death induced by bafilomycin A1 and tamoxifen, suggesting that bafilomycin A1-mediated CHOP activation sensitizes to tamoxifen. In addition, we found that bafilomycin A1 enhances TRAIL-induced cell death in breast cancer cells. Furthermore, we showed that combination of vATPase inhibitors with tamoxifen also effectively induced cell death in HER2- and ERĪ±-overexpressing breast cancer cells. Overall, our results demonstrate that inhibition of vATPase can potentiate the apoptotic effects of tamoxifen through up-regulation of CHOP.
- Subjects :
- Vacuolar Proton-Translocating ATPases
medicine.medical_specialty
Programmed cell death
Biophysics
Estrogen receptor
Apoptosis
Breast Neoplasms
CHOP
Biochemistry
chemistry.chemical_compound
Breast cancer
Cell Line, Tumor
Internal medicine
polycyclic compounds
medicine
Humans
skin and connective tissue diseases
Molecular Biology
Cell Death
Chemistry
Bafilomycin
Drug Synergism
Cell Biology
ATP6V0C
medicine.disease
Up-Regulation
Tamoxifen
Endocrinology
Gene Knockdown Techniques
MCF-7 Cells
Cancer research
Female
biological phenomena, cell phenomena, and immunity
Transcription Factor CHOP
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 437
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....b1f21312d4d09c7c3139bad771de29ed