The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops, on cell growth and tumorigenesis in human pancreatic cancer - 24/07/15

Doi : 10.1016/j.biopha.2015.05.020

Weiliang Jiang ^a,^{^{1
These authors contributed equally to this paper.},}^{^{4
Tel.: +86 18817821652.}} , Senlin Zhao ^b,^{^{1
These authors contributed equally to this paper.},}^{^{5
Tel.: +86 18817821660.}} , Ling Xu ^c,^{^{1
These authors contributed equally to this paper.},}^{^{6
Tel.: +86 18121226823.}} , Yingying Lu ^a,^{^{7
Tel.: +86 18621583036.}} , Zhanjun Lu ^a,^{^{8
Tel.: +86 13564326372.}} , Congying Chen ^a,^{^{9
Tel.: +86 18116149147.}} , Jianbo Ni ^a,^{^{10
Tel.: +86 13611787308.}} , Rong Wan ^a,^{^{2
Tel.: +86 13167018998; fax: +86 21 63241377.},}^⁎ , Lijuan Yang ^a,^{^{3
Tel.: +86 18917683428; fax: +86 21 63241377.},}^⁎
^a Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100, Hai Ning Road, Shanghai 200080, China
^b Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
^c Department of Gastroenterology, Shanghai Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

^⁎Corresponding authors.

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Abstract

Pancreatic cancer (PC) is one of the most lethal human malignancies worldwide. Here, we demonstrated that xanthohumol (XN), the most abundant prenylated chalcone isolated from hops, inhibited the growth of cultured PC cells and their subcutaneous xenograft tumors. XN treatment was found to induce cell cycle arrest and apoptosis of PC cells (PANC-1, BxPC-3) by inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of its downstream targeted genes cyclinD1, survivin, and Bcl-xL at the messenger RNA level, which involved in regulation of apoptosis and the cell cycle. Overall, our results suggested that XN presents a promising candidate therapeutic agent against human PC and the STAT3 signaling pathway is its key molecular target.

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Keywords : Xanthohumol, Pancreatic cancer, STAT3 signaling

Plan

Introduction

Materials and methods

Cells, reagents and animals

Cell viability assay

2-D colony formation assay

3-D colony formation assay

Apoptosis assay

Cell cycle analysis

Western blotting

Real-time polymerase chain reaction (PCR)

Hematoxylin and eosin (HE), immunohistochemical (IHC), and immunofluorescence (IF) staining

PANC-1 subcutaneous xenograft animal model

Statistical analysis

Results

Effects of XN on the viability and colony formation of PC cell lines in vitro

Effects of XN on apoptosis and cell cycle of PC cell lines in vitro

XN suppresses PC growth in xenograft models

XN induces cell death through inactivating STAT3 signaling in PANC-1 cells

Discussion and conclusion

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Vol 73

P. 40-47 - juillet 2015 Retour au numéro

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The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops, on cell growth and tumorigenesis in human pancreatic cancer - 24/07/15

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