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- W917967032 abstract "Activating K-Ras is present in 90, 50 and 25% of pancreatic, colorectal and lung cancers, respectively, making them refractive to chemotherapies. Tumors with Ras mutations are challenging to drug, leading to poor prognoses. We hypothesize that polyisoprenylated cysteinyl amides inhibitors (PCAIs) can be effectively used to target and disrupt Ras signaling resulting in potentially very effective new therapies. To test this, MIAPaCa-2, Panc10-05, Caco-2 and A549 human cancer cells were treated with PCAIs for their effects on cell viability, proliferation, apoptosis and migration. The PCAIs inhibited MIAPaCa-2, Panc10.05, Caco-2 and A549 cell viability and proliferation with EC50 values ranging from 2.0 to 6.0, 1.8 to 3.3, 0.2 to 4.0 and 0.4 to 10 µM, respectively. Ethidium bromide/acridine orange analysis suggests an apoptotic cell death mechanism while annexin v/propidium iodide flow cytometry analysis revealed cell arrest at the G0/G1 phase. Submicromolar concentrations of PCAIs significantly inhibited MIAPaCa-2 cell migration in the wound-healing assay. The effect on migration appeared to be linked to the disruption of filamentous actin organization as observed with phalloidin staining and transfections with a plasmid expressing an RFP-tagged F-actin marker protein. The potency of PCAIs in K-Ras mutant cells is likely due to the disruption of signaling by Ras and related monomeric G-proteins such as RhoA/B. PCAIs might therefore represent attractive therapeutic molecules for cancers with activating Ras mutations and hyperactive G-proteins. Supported by the NIMHD of the NIH under Award Number G12 MD007582" @default.
- W917967032 created "2016-06-24" @default.
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- W917967032 date "2015-04-01" @default.
- W917967032 modified "2023-09-25" @default.
- W917967032 title "Polyisoprenylated Cysteinyl Amides Induce Apoptosis and Inhibit Proliferation and Migration of Human K‐Ras Mutant Cancer cells" @default.
- W917967032 doi "https://doi.org/10.1096/fasebj.29.1_supplement.563.10" @default.
- W917967032 hasPublicationYear "2015" @default.
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