Influence of docosahexaenoic acid on cisplatin resistance in a human small cell lung carcinoma cell line.
J Natl Cancer Inst
; 81(14): 1069-75, 1989 Jul 19.
Article
in En
| MEDLINE
| ID: mdl-2544740
ABSTRACT
In a sensitive, human, small cell lung carcinoma cell line (GLC4) and a cisplatin (CP)-resistant subline (GLC4-CP), the effect of co-culturing with docosahexaenoic acid (DCHA) on CP cytotoxicity was studied. Cells were cultured for 4 days, with 32 microM of DCHA added on days 1 and 3. Incorporation of DCHA into the cellular phospholipids was demonstrated by fatty acid analysis. Supplementation with DCHA led to almost a threefold decrease of resistance in GLC4-CP and had no influence on CP cytotoxicity in GLC4. After culturing with DCHA, cellular platinum (Pt); total Pt bound to DNA; and Pt-GG, Pt-AG, G-Pt-G, and Pt-GMP adduct contents increased in both lines, whereas interstrand cross-link formation was elevated only in GLC4-CP. These experiments demonstrate that DCHA reduces CP resistance. Although an effect on cellular membranes resulting in an increased CP uptake apparently was present, this mechanism does not seem to be responsible for resistance modulation. Rather, an effect on nuclear, probably DNA-related, structures is likely and leads to an increased formation of interstrand cross-links in GLC4-CP.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Docosahexaenoic Acids
/
Cisplatin
/
Carcinoma, Small Cell
/
Lung Neoplasms
Limits:
Humans
Language:
En
Journal:
J Natl Cancer Inst
Year:
1989
Type:
Article
Affiliation country:
Netherlands