title: Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase.
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.
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge St., PO Box 19626, Springfield, IL 62794-9626, USA.
authors.forename: Puspa R
authors.initials: PR
authors.lastname: Pandey
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okuda
authors.forename: Misako
authors.initials: M
authors.lastname: Watabe
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Pai
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Aya
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirota
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Koeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kashiwaba
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Toshimi
authors.initials: T
authors.lastname: Chiba
authors.forename: Masaki
authors.initials: M
authors.lastname: Endo
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Susumu
authors.initials: S
authors.lastname: Tanji
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Wilber
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D064550:Death-Associated Protein Kinases; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C090121:BNIP3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D013267:Stilbenes; D064429:Fatty Acid Synthases; C579104:DAPK2 protein, human; D064550:Death-Associated Protein Kinases; C579103:dapk2 protein, mouse; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000077185:Resveratrol