Abstract | BACKGROUND: METHODS: The effectiveness of RRR-alpha- and RRR- gamma-tocopherol at inhibiting cell growth and inducing apoptosis in colon cancer cell lines with varying molecular characteristics (SW480, HCT-15, HCT-116 and HT-29) and primary colon cells (CCD-112CoN, nontransformed normal phenotype) was studied. Colon cells were treated with and without RRR-alpha- or RRR- gamma-tocopherol using varying tocopherol concentrations and time intervals. Cell proliferation and apoptosis were measured using the trypan blue assay, annexin V staining, DNA laddering and caspase activation. RESULTS: Treatment with RRR- gamma-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR- alpha-tocopherol did not. Further, RRR- gamma-tocopherol treatment showed no cytotoxicity to normal colon cells CCD-112CoN at the highest concentration and time point tested. RRR- gamma-tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not caspase 9. Differences in the percentage cell death and apoptosis were observed in different cell lines suggesting that molecular differences in these cell lines may influence the ability of RRR- gamma-tocopherol to induce cell death. CONCLUSION: This is the first study to demonstrate that multiple colon cancer cell lines containing varying genetic alterations will under go growth reduction and apoptosis in the presence of RRR- gamma-tocopherol without damage to normal colon cells. The amount growth reduction was dependent upon the molecular signatures of the cell lines. Since RRR- gamma-tocopherol is effective at inhibition of cell proliferation at both physiological and pharmacological concentrations dietary RRR- gamma-tocopherol may be chemopreventive, while pharmacological concentrations of RRR- gamma-tocopherol may aid chemotherapy without toxic effects to normal cells demonstrated by most chemotherapeutic agents.
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Authors | Sharon E Campbell, William L Stone, Steven Lee, Sarah Whaley, Hongsong Yang, Min Qui, Paige Goforth, Devin Sherman, Derek McHaffie, Koyamangalath Krishnan |
Journal | BMC cancer
(BMC Cancer)
Vol. 6
Pg. 13
(Jan 17 2006)
ISSN: 1471-2407 [Electronic] England |
PMID | 16417629
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antioxidants
- Protein Isoforms
- gamma-Tocopherol
- alpha-Tocopherol
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Topics |
- Antioxidants
(pharmacology)
- Apoptosis
(drug effects)
- Cell Proliferation
(drug effects)
- Chemoprevention
- HCT116 Cells
- HT29 Cells
- Humans
- Protein Isoforms
- alpha-Tocopherol
(pharmacology)
- gamma-Tocopherol
(pharmacology)
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