Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS-transformed human colon cells

Faiy H. Psahoulia, Sophy Moumtzi, Michael L. Roberts, Takehiko Sasazuki, Senji Shirasawa, Alexander Pintzas

研究成果: ジャーナルへの寄稿学術誌査読

120 被引用数 (Scopus)

抄録

Several food polyphenols act as chemopreventers by reducing the incidence of many types of cancer, especially in colon epithelia. In this study, we have investigated whether the flavonoid quercetin can modulate cell proliferation and survival by targeting key molecules and/ or biological processes responsible for tumor cell properties. The effect of quercetin on the expression of Ras oncoproteins was specifically studied using systems of either constitutive or conditional expression of oncogenic RAS in human epithelial cells. Our findings suggest that quercetin inhibits cell viability as well as cancer cell properties like anchorageindependent growth. These findings were further supported at the molecular level, since quercetin treatment resulted in a preferential reduction of Ras protein levels in cell lines expressing oncogenic Ras proteins. Notably, in cells that only express wildtype Ras or in those where the oncogenic Ras allele was knocked out, quercetin had no evident effects upon Ras levels. We have shown that quercetin drastically reduces half-life of oncogenic Ras but has no effect when the cells are treated with a proteasome inhibitor. Moreover, in Ha-RAS-transformed cells, quercetin induces autophagic processes. Since quercetin downregulates the levels of oncogenic Ras in cancer cells, we propose that this flavonoid could act as a chemopreventive agent for cancers with frequent mutations of RAS genes.

本文言語英語
ページ(範囲)1021-1031
ページ数11
ジャーナルCarcinogenesis
28
5
DOI
出版ステータス出版済み - 5月 2007
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 癌研究

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