Journal
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
Volume 33, Issue 11, Pages -Publisher
WILEY
DOI: 10.1002/jbt.22399
Keywords
5-fluorouracil; apoptosis; cancer; combination therapy; gamma-tocopherol
Categories
Funding
- Sarab Faculty of Medicine, Sarab, Iran [97315]
Ask authors/readers for more resources
Resistance to chemotherapy with 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC) is the major obstacle to reach the maximum efficiency of CRC treatment. Combination therapy has emerged as a novel anticancer strategy. The present study evaluates the cotreatment of gamma-tocopherol and 5-FU in enhancing the efficacy of chemotherapy against HT-29 colon cancer cells. Cytotoxic effect of this combination was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and a synergistic effect was evaluated by a combination index technique. Nuclear morphology was studied via 4 ',6-diamidino-2-phenylindole staining and flow cytometric assays were conducted to identify molecular mechanisms of apoptosis and cell cycle progression. We investigated the expression of Cyclin D1, Cyclin E, Bax, and Bcl-2 by a quantitative real-time polymerase chain reaction. The IC50 values for 5-FU and gamma-tocopherol were 21.8 +/- 2.5 and 14.4 +/- 2.6 mu M, respectively, and also this combination therapeutic increased the percentage of apoptotic cells from 35% +/- 2% to 40% +/- 4% (P < .05). Furthermore, incubation HT-29 colon cells with combined concentrations of two drugs caused significant accumulation of cells in the subGsubG1 phase. Our results presented the combination therapy with 5-FU and gamma-tocopherol as a novel therapeutic approach, which can enhance the efficacy of chemotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available