Faculty Collaboration Database

Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma. PLoS One 2015;10(5):e0127464

Date

05/27/2015

Pubmed ID

26011160

Pubmed Central ID

PMC4444108

DOI

10.1371/journal.pone.0127464

Scopus ID

2-s2.0-84949649299 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3) and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1). XN concentrations of 5 μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

Author List

Kunnimalaiyaan S, Sokolowski KM, Balamurugan M, Gamblin TC, Kunnimalaiyaan M

Author

Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apoptosis
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Proliferation
Cell Survival
Flavonoids
Humans
Liver Neoplasms
Propiophenones
Receptors, Notch
Signal Transduction
Tumor Stem Cell Assay