Effect of omega-3 fatty acid (docosahexanoic acid) on BRCA1 gene expression and growth in MCF-7 cell line.
Recently, we have demonstrated that omega-6 fatty acid linoleic acid (LA) in presence of estradiol (E2) enhances proliferation and anchorage independent growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. Since omega-3 fatty acid (docosahexanoic acid, DHA) is known to block the promoting effect of omega-6 polyunsaturated fatty acid (LA), we wanted to see whether addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA + E2 and any alteration of BRCA1 mRNA expression could be seen in DHA treated culture. Experiments on MCF-7 cells with DHA revealed both decrease in proliferation and anchorage independency as compared to controls; while no change of BRCA1 mRNA expression was observed. Further, when DHA was administered to cells along with LA + E2, no change in BRCA1 expression was observed, however, a marked decrease in proliferation and soft agar colony formation was evident, indicating inhibition of MCF-7 cells following DHA treatment. Flow cytometric analysis showed that DHA treated cells either alone or in combination with LA + E2 induced marked G1/S and G2/M arrest of the cells, suggesting the inhibitory effect of DHA at this phase of cell cycle. However, neither typical DNA ladder nor fragmented nuclei or apoptotic bodies were observed, ruling out presence of apoptosis following DHA treatment.
Kachhap
S K
SK
Cell Biology Division, Immunology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai-400012, India.
Dange
P P
PP
Santani
R H
RH
Sawant
S S
SS
Ghosh
S N
SN
D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
D019313:BRCA1 Protein; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D019787:Linoleic Acid