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Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.6 P.441~447

10.1631/jzus.B0740640


Increased fatty acid synthase as a potential therapeutic target in multiple myeloma


Author(s):  Wei-qin WANG, Xiao-ying ZHAO, Hai-yan WANG, Yun LIANG

Affiliation(s):  Department of Hematology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China

Corresponding email(s):   ZRXZ@zju.edu.cn

Key Words:  Fatty acid synthase (FAS), Cerulenin, Apoptosis, Multiple myeloma


Wei-qin WANG, Xiao-ying ZHAO, Hai-yan WANG, Yun LIANG. Increased fatty acid synthase as a potential therapeutic target in multiple myeloma[J]. Journal of Zhejiang University Science B, 2008, 9(6): 441~447.

@article{title="Increased fatty acid synthase as a potential therapeutic target in multiple myeloma",
author="Wei-qin WANG, Xiao-ying ZHAO, Hai-yan WANG, Yun LIANG",
journal="Journal of Zhejiang University Science B",
volume="9",
number="6",
pages="441~447",
year="2008",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0740640"
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%T Increased fatty acid synthase as a potential therapeutic target in multiple myeloma
%A Wei-qin WANG
%A Xiao-ying ZHAO
%A Hai-yan WANG
%A Yun LIANG
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 6
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%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0740640

TY - JOUR
T1 - Increased fatty acid synthase as a potential therapeutic target in multiple myeloma
A1 - Wei-qin WANG
A1 - Xiao-ying ZHAO
A1 - Hai-yan WANG
A1 - Yun LIANG
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 6
SP - 441
EP - 447
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0740640


Abstract: 
Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors. In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPMI8226. U266 cells were treated with cerulenin at various concentrations (5 to 320 µg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. apoptosis was evaluated by dual Annexin V/PI (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 (g/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPMI8226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPMI8226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 µg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V+/PI cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V+/PI+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.

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Reference

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