Abstract
Autophagy, a process of regulated turnover of cellular constituents, is essential for normal growth control but may be defective under pathological conditions. The Ras/PI3K/mTOR signaling pathway negatively regulates autophagy. Ras signaling has been documented in a large number of human cancers. In this in-vitro study we examined the effect of the Ras inhibitor Salirasib (S-trans, trans-farnesylthiosalicylic acid; FTS) on autophagy induction and cell viability. We show that Ras inhibition by FTS induced autophagy in several cell lines, including mouse embryonic fibroblasts and the human cancer cell lines HeLa, HCT-116 and DLD-1. The autophagy induced by FTS seems to inhibit the cell death induced by FTS, since in the absence of autophagy the death of FTS-treated cells was enhanced. Therefore, inhibition of autophagy may promote the inhibition of tumor cell growth and the cell death mediated by FTS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Autophagy / drug effects*
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Autophagy-Related Protein 5
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Cell Line, Tumor
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Embryo, Mammalian / cytology
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Farnesol / analogs & derivatives*
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Farnesol / pharmacology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HCT116 Cells
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HeLa Cells
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Humans
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Immunoblotting
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Mice
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Mice, Knockout
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Microscopy, Fluorescence
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Microtubule-Associated Proteins / deficiency
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Salicylates / pharmacology*
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ras Proteins / antagonists & inhibitors*
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ras Proteins / metabolism
Substances
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Antineoplastic Agents
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Atg5 protein, mouse
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Autophagy-Related Protein 5
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Microtubule-Associated Proteins
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Salicylates
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farnesylthiosalicylic acid
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Green Fluorescent Proteins
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Farnesol
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ras Proteins