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Adjuvant therapy with γ‐tocopherol‐induce apoptosis in HT‐29 colon cancer via cyclin‐dependent cell cycle arrest mechanism
Author(s) -
Bazzaz Roya,
Bijanpour Hossain,
Pirouzpanah Seyed M. B.,
Yaghmaei Parichehreh,
Rashtchizadeh Nadereh
Publication year - 2019
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22399
Subject(s) - cyclin d1 , apoptosis , colorectal cancer , cell cycle , cancer research , combination therapy , chemotherapy , combination chemotherapy , pharmacology , chemistry , cancer , medicine , biochemistry
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 γ‐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 IC 50 values for 5‐FU and γ‐tocopherol were 21.8 ± 2.5 and 14.4 ± 2.6 μM, 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 γ‐tocopherol as a novel therapeutic approach, which can enhance the efficacy of chemotherapy.