Conjugated linoleic acid induces apoptosis in MDA-MB-231 breast cancer cells through ERK/MAPK signalling and mitochondrial pathway.
We investigated the molecular mechanisms involved in the anti-proliferative activity exerted by conjugated linoleic acid (CLA) on the estrogen unresponsive MDA-MB-231 human breast cancer cell line. The effects on cell proliferation, cell cycle progression and induction of apoptosis were examined. CLA caused the reduction of cell proliferation along with the accumulation of cells in the S phase of the cycle. The occurrence of apoptosis in these cells was indicated by flow cytometry data and further confirmed by the onset of cells with morphological features typical of apoptosis. ERK1/2 reduction and upregulation of pro-apoptotic protein Bak were induced. These events were associated with: (a) reduced levels of the anti-apoptotic protein Bcl-x(L), (b) the translocation of cytochrome c from the mitochondria to the cytosol, (c) the cleavage of pro-caspase-9 and pro-caspase-3. From the above data, we are induced to think that CLA may trigger apoptosis in the estrogen unresponsive MDA-MB-231 cell line via mechanisms involving above all the mitochondrial pathway.
Miglietta
Antonella
A
Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125 Turin, Italy. antoinella.miglietta@unito.it
Bozzo
Francesca
F
Bocca
Claudia
C
Gabriel
Ludovica
L
Trombetta
Antonella
A
Belotti
Simona
S
Canuto
Rosa A
RA
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D044243:Linoleic Acids, Conjugated; D045304:Cytochromes c; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases