Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo.

Abstract:

:Isoxanthohumol (IXN), a prenylated flavonoid from hops, exhibits diverse biological activities, e.g. antitumor, antiinflammatory, antioxidant and antiangiogenic. In this study, the effect of IXN is evaluated on two melanoma cell lines with dissimilar molecular background, B16 and A375. The treatment of both cell lines with IXN resulted in dose-dependent decrease of cell viability. Abolished viability was in correlation with changed morphology and loss of dividing potential indicating phenotypical alteration of both tested cell lines. While modified B16 cells underwent the process of non-classic differentiation followed by tyrosinase activity without enhancement of melanin content, inhibition of Notch 1, β-catenin and Oct-3/4 was observed in A375 cells indicating loss of their pluripotent characteristics. In parallel with this, distinct subpopulations in both cell cultures entered the process of programmed cell death-apoptosis in a caspase independent manner. The described changes in cultures upon exposure to IXN could be connected with the suppression of reactive oxygen (ROS) and nitrogen species (RNS) induced by the drug. Despite the differences in which IXN promoted modifications in the upper part of the PI3K/Akt and MEK-ERK signaling pathways between B16 and A375 cells, p70S6K and its target S6 protein in both types of melanoma cells, after transient activation, became inhibited. In addition to direct input of IXN on cell viability, this study for the first time shows that IXN strongly sensitizes melanoma cells to the treatment with paclitaxel in vivo, in concordance with data obtained in vitro on B16 cells as well as their highly invasive F10 subclone.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Krajnović T,Kaluđerović GN,Wessjohann LA,Mijatović S,Maksimović-Ivanić D

doi

10.1016/j.phrs.2016.01.011

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

62-73

eissn

1043-6618

issn

1096-1186

pii

S1043-6618(16)00018-9

journal_volume

105

pub_type

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