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Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i) in MCF-7 Breast Cancer Cells
- Source :
- Cancers, Volume 6, Issue 4, Pages 2243-2258, Cancers, Vol 6, Iss 4, Pp 2243-2258 (2014)
- Publication Year :
- 2014
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2014.
-
Abstract
- Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i) in breast cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i) was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong negative correlation (r = −0.713) to viability. Pharmacological modulators 2-APB (50 μM), Nimodipine (10 μM), Caffeine (10 mM), SKF 96365(20 μM) were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells.
- Subjects :
- Cancer Research
Programmed cell death
Auranofin
chemistry.chemical_element
Pharmacology
Calcium
lcsh:RC254-282
Calcium in biology
Article
chemistry.chemical_compound
breast cancer
medicine
intracellular calcium
Voltage-dependent calcium channel
business.industry
apoptosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
anticancer drugs
Oncology
chemistry
Apoptosis
Cancer cell
cytotoxicity
Trypan blue
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....1b9145b8c4c745034ef06d15a55729e2
- Full Text :
- https://doi.org/10.3390/cancers6042243