Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells

Yinlin Ge, Zhihong Chen, Zhao B. Kang, Joanne Cluette-Brown, Michael Laposata, Jing X. Kang

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background: Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. Materials and Methods: Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. Results: Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. Conclusion: The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment.

Original languageEnglish (US)
Pages (from-to)537-543
Number of pages7
JournalAnticancer Research
Volume22
Issue number2 A
StatePublished - 2002
Externally publishedYes

Fingerprint

Omega-3 Fatty Acids
Breast Neoplasms
Lipids
Growth
Genes
Fatty Acid Desaturases
Omega-6 Fatty Acids
Fats
C elegans fat-1 protein
Neoplasms
Eicosanoids
MCF-7 Cells
Unsaturated Fatty Acids
Adipocytes
Adenoviridae
Cell Death
Cell Proliferation

Keywords

  • Breast cancer
  • Gene transfer
  • n-3 fatty acid desaturase
  • n-6/n-3 fatty acid ratio
  • Proliferation and apopotosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. / Ge, Yinlin; Chen, Zhihong; Kang, Zhao B.; Cluette-Brown, Joanne; Laposata, Michael; Kang, Jing X.

In: Anticancer Research, Vol. 22, No. 2 A, 2002, p. 537-543.

Research output: Contribution to journalArticle

Ge, Yinlin ; Chen, Zhihong ; Kang, Zhao B. ; Cluette-Brown, Joanne ; Laposata, Michael ; Kang, Jing X. / Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. In: Anticancer Research. 2002 ; Vol. 22, No. 2 A. pp. 537-543.
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AU - Cluette-Brown, Joanne

AU - Laposata, Michael

AU - Kang, Jing X.

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AB - Background: Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. Materials and Methods: Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. Results: Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. Conclusion: The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment.

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KW - Proliferation and apopotosis

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