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Chalcones bearing a 3,4,5-trimethoxyphenyl motif are capable of selectively inhibiting oncogenic K-Ras signaling.


ABSTRACT: Ras proteins are small GTPases which regulate cellular proliferation, differentiation, and apoptosis. Constitutively active mutant Ras are expressed in ~15-20% human cancers, and K-Ras mutations account for ~85% of all Ras mutations. Despite the significance of Ras proteins in refractory cancers, there is no anti-Ras drug available in clinic. Since K-Ras must interact with the plasma membrane (PM) for biological activity, inhibition of the K-Ras/PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we discovered chalcones 1 and 8 exhibit anti-K-Ras activity, and show that the compounds mislocalize K-Ras from the PM and block oncogenic K-Ras signal output. Also, 1 inhibits the growth of K-Ras-driven human cancer cells. Our data suggest that 1 could be a promising starting point for developing anti-K-Ras cancer drug.

SUBMITTER: Kovar SE 

PROVIDER: S-EPMC7216516 | biostudies-literature |

REPOSITORIES: biostudies-literature

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