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Updated: Aug 11, 2026
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
Published on: October 5, 2020
RRR-alpha-tocopherol succinate down-regulates oncogenic Ras signaling
Sreenivasa Donapaty1, Somaja Louis, Elizabeth Horvath
1Gastrointestinal Tumor Program, Division of Gastrointestinal Tumors, Department of Interdisciplinary Oncology, University of South Florida, Tampa, Florida 33612, USA.
Molecular Cancer Therapeutics
|March 1, 2006
Summary
Alpha-Tocopherol succinate (TS), a vitamin E analogue, inhibits cancer cell growth by down-regulating Ras signaling pathways. This suggests TS has potential as a chemopreventive and therapeutic agent for Ras-dependent tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Alpha-Tocopherol succinate (TS), a vitamin E analogue, exhibits anti-cancer properties in various models.
- Oncogenic Ras signaling pathways are frequently activated in cancer and drive tumor growth and survival.
Purpose of the Study:
- To investigate the role of oncogenic Ras modulation in the anti-cancer activity of TS.
- To elucidate the specific signaling pathways targeted by TS in Ras-transformed cells.
Main Methods:
- Utilized NIH3T3 cell lines engineered to express oncogenic K-Ras or H-Ras.
- Assessed the effects of TS on cell proliferation, apoptosis, protein levels (Ras, phospho-Akt, phospho-Erk1/2), and transcriptional targets (c-Myc, cyclin D1, E2F1).
- Examined TS activity in endogenous oncogenic Ras-expressing human cancer cell lines (HCT 116, MDA-MB-231).
Main Results:
- TS inhibited proliferation and induced apoptosis in Ras-transformed cells, but not in control cells.
- TS treatment decreased Ras protein levels and suppressed phospho-Akt and phospho-Erk1/2 signaling in oncogenic Ras-expressing cells.
- TS down-regulated key Ras transcriptional targets and demonstrated similar effects in human colon and breast cancer cells.
Conclusions:
- TS exerts its anti-cancer effects, at least in part, by down-regulating Ras signaling pathways, including Mek/Erk and phosphoinositide-3-kinase/Akt.
- These findings support the investigation of TS for chemoprevention and therapy in Ras-dependent cancers.
- Phospho-Erk and phospho-Akt may serve as biomarkers for TS activity.
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