Preclinical Study

Breast Cancer Research and Treatment

, Volume 130, Issue 2, pp 387-398

First online:

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase

  • Puspa R. PandeyAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Hiroshi OkudaAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Misako WatabeAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Sudha K. PaiAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Wen LiuAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Aya KobayashiAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Fei XingAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Koji FukudaAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
  • , Shigeru HirotaAffiliated withIwate Medical University, School of Medicine
    • , Tamotsu SugaiAffiliated withIwate Medical University, School of Medicine
    • , Go WakabayashiAffiliated withIwate Medical University, School of Medicine
    • , Keisuke KoedaAffiliated withIwate Medical University, School of Medicine
    • , Masahiro KashiwabaAffiliated withIwate Medical University, School of Medicine
    • , Kazuyuki SuzukiAffiliated withIwate Medical University, School of Medicine
    • , Toshimi ChibaAffiliated withIwate Medical University, School of Medicine
    • , Masaki EndoAffiliated withIwate Medical University, School of Medicine
    • , Tomoaki FujiokaAffiliated withIwate Medical University, School of Medicine
    • , Susumu TanjiAffiliated withIwate Medical University, School of Medicine
    • , Yin-Yuan MoAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
    • , Deliang CaoAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine
    • , Andrew C. WilberAffiliated withDepartment of Surgery, Southern Illinois University School of Medicine
    • , Kounosuke WatabeAffiliated withDepartment of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine Email author 

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Abstract

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24/CD44+/ESA+) that were isolated from both ER+ and ER− breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol.

Keywords

Fatty acid synthase Lipogenesis Breast cancer Stem-like cells Apoptosis