title: Cucurbitacin B and cucurbitacin I suppress adipocyte differentiation through inhibition of STAT3 signaling.
abstract: Cucurbitacin B, a member of the cucurbitaceae family, can act as a STAT3 signaling inhibitor to regulate the growth of hepatocellular carcinoma. STAT3 signaling has been shown to inhibit adipocyte differentiation through C/EBPα and PPARγ. Based on these studies, we hypothesized that cucurbitacin B would prevent PPARγ mediated adipocyte differentiation through STAT3 signaling. To test this hypothesis, mesenchymal C3H10T1/2 and 3T3-L1 preadipocyte cells were treated with a sub-cytotoxic concentration of cucurbitacin B. Cucurbitacin B treatment inhibits lipid accumulation and expression of adipocyte markers including PPARγ and its target genes in a dose-dependent manner. Cucurbitacin B treatment impairs STAT3 signaling as manifested by reduced phosphorylation of STAT3 and suppression of STAT3 target gene expression in preadipocytes. The anti-adipogenic effects of cucurbitacin B are significantly blunted in cells with STAT3 silenced by introducing small interfering RNA. Finally, our data show that cucurbitacin I, another cucurbitacin family member, also inhibits adipocyte differentiation by suppressing STAT3 signaling. Together, our data suggest the possibility of utilizing cucurbitacins as a new strategy to treat metabolic diseases and implicate STAT3 as a new target for the development of functional foods and drugs.
authors: Department of Food Science and Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Cho-Rong
authors: CR
authors: Seo
authors: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors: Dong Kwon
authors: DK
authors: Yang
authors: Department of Food Science and Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: No-Joon
authors: NJ
authors: Song
authors: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Ui Jeong
authors: UJ
authors: Yun
authors: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: A-Ryeong
authors: AR
authors: Gwon
authors: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Dong-Gyu
authors: DG
authors: Jo
authors: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Jae Youl
authors: JY
authors: Cho
authors: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Keejung
authors: K
authors: Yoon
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors: Jee-Yin
authors: JY
authors: Ahn
authors: Functional Food Center, Korea Institute of Science and Technology, Gangneung Institute, Gangwon-do 210-340, Republic of Korea.
authors: Chu Won
authors: CW
authors: Nho
authors: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors: Woo Jin
authors: WJ
authors: Park
authors: Department of Horticulture, Sunchon National University, 413 Jungangno, Suncheon, Jeonnam 540-742, Republic of Korea.
authors: Seung Yul
authors: SY
authors: Yang
authors: Department of Food Science and Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: kwpark@skku.edu.
authors: Kye Won
authors: KW
authors: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014315:Triterpenes; C041246:cucurbitacin B; C038106:cucurbitacin I
keywords: Adipocyte differentiation; Cucurbitacin B; Cucurbitacin I; PPARγ; STAT3