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

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Abstract

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.

Original languageEnglish
Pages (from-to)1021-1031
Number of pages11
JournalCarcinogenesis
Volume28
Issue number5
DOIs
Publication statusPublished - May 1 2007
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Psahoulia, F. H., Moumtzi, S., Roberts, M. L., Sasazuki, T., Shirasawa, S., & Pintzas, A. (2007). Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS-transformed human colon cells. Carcinogenesis, 28(5), 1021-1031. https://doi.org/10.1093/carcin/bgl232