An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines.
Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.
Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Torino, Italy.
Marina
M
Maggiora
Mauro
M
Bologna
Maria Paola
MP
Cerù
Laura
L
Possati
Angelo
A
Angelucci
Anna
A
Cimini
Antonella
A
Miglietta
Francesca
F
Bozzo
Chiara
C
Margiotta
Guiliana
G
Muzio
Rosa Angela
RA
Canuto
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy; D009336:Necrosis / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D019787:Linoleic Acid