Growth inhibition of osteosarcoma cell MG-63 by a mixture of trans,trans conjugated linoleic acid isomers: possible mechanistic actions.
The growth inhibitory effect of a mixture of t,t conjugated linoleic acid isomers (t,t CLA) was investigated in the human osteosarcoma cell MG-63, with references to c9,t11 and t10,c12 CLA isomers. The t,t CLA effectively induced a cytotoxic effect in a time-dependent (0 to 6 d) and concentration-dependent (0 to 40 microM) manner, as compared to the reference and control treatments. The apoptosis and cell cycle related parameters were measured on the cells treated with 40 microM t,t CLA for 4 d. Flow cytometric analysis revealed that the t,t CLA treatment effectively increased the proportion of apoptotic cells with a low DNA content (sub G0/G1) and a marked loss of cells from the G0/G1 phase of the cell cycle, relative to other treatments. The occurrence of the characteristic morphological changes and DNA fragmentation confirmed the apoptosis. The level of Bax protein was increased, whereas the Bcl-2 expression was reduced. In addition, cytochrome c was released from the mitochondria into the cytosol, and the activation of caspase-3 led to the cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, the composition of linoleic and arachidonic acids in membrane was decreased by increase in t,t CLA. These findings suggest that t,t CLA incorporation in membrane activates a mitochondria-mediated apoptosis pathway that can enhance the antiproliferative effect of t,t CLA in the osteosarcoma cells.
Kim
Y S
YS
Division of Applied Life Sciences, Graduated School, and Institute of Agriculture & Life Science, Gyeongsang National University, Jinju 660-701, Korea.
Cerbo
R M
RM
Hah
C K
CK
Bahn
K N
KN
Kim
J O
JO
Ha
Y L
YL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy*; D013997:Time Factors; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D044243:Linoleic Acids, Conjugated; D051028:bcl-2-Associated X Protein