Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human colon cancer cells: Involvement of the PI3K/Akt and MAP kinase pathways.

Abstract:

:Methyl 3,5-dicaffeoyl quinate (MDQ) is a flavonoid glucoside found in several plants that scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and peroxynitrite, and inhibits the formation of cholesteryl ester hydroperoxide during the copper ion-induced oxidation of blood plasma in rats. In this study, MDQ inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner as detected by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), trypan blue exclusion, and flow cytometric assays. Western blot analysis showed that apoptosis was dependent on caspase-3 activity. PARP cleavage and the cytosolic release of cytochrome c from mitochondria increased significantly. In addition, these events were accompanied by a collapse in the mitochondrial membrane potential and a decreased Bcl-2/Bax ratio. Furthermore, the MDQ-induced G(0)/G(1) arrest was correlated with an increase in p27 and a decrease in cyclin D1 and p53. MDQ also inhibited the phosphorylation of PI3K/Akt and ERK; significantly reduced NF-κB; and in general displayed a significant anti-proliferative effect via a cell cycle arrest and apoptotic induction in HT-29 cells. These results suggest that MDQ has therapeutic potential against human colon carcinoma.

journal_name

Chem Biol Interact

authors

Hu W,Shen T,Wang MH

doi

10.1016/j.cbi.2011.08.006

subject

Has Abstract

pub_date

2011-10-15 00:00:00

pages

48-57

issue

1

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(11)00258-4

journal_volume

194

pub_type

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