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RRR-alpha-tocopheryl succinate induces apoptosis in avian retrovirus-transformed lymphoid cells.
Nutr Cancer. 1996; 25(1):9-26.NC

Abstract

The RRR-alpha-tocopheryl succinate form of vitamin E [vitamin E succinate (VES)] inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner, blocks the cells in the G2/M cell cycle phase, and induces the cells to undergo apoptosis. Apoptosis was documented by demonstrating changes that are characteristic of this type of cell death, including morphological analyses of chromatin condensation by 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining using scanning confocal and traditional fluorescent microscopy; flow cytometry analyses of propidium iodide-labeled DNA showing fragmented DNA as a pre-G1 peak; two-color flow cytometry analyses of intact cells labeled first by the TUNEL procedure (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeled DNA stained with fluorescein isothiocyanate-labeled avidin) and then by propidium iodide demonstrating fragmented DNA; and electrophoresis of DNA showing a DNA ladder created by internucleosomal DNA fragmentation. The percentage of apoptotic cells was determined by DAPI staining and showed 11%, 27%, and 49% of cells to be apoptotic after treatment with 10 micrograms/ml VES for one, two, and three days, respectively. Analyses of mRNA levels of genes that have been implicated in the apoptotic process, namely, bcl-2, c-myc, and c-jun, revealed no change in bcl-2, decreases in c-myc mRNA levels after 36 hours of treatment, and increases in c-jun mRNA levels within four hours after treatment. Western immunoblotting analyses of protein levels for the transcription factors c-Myc and c-Jun showed normal levels of c-Myc at early time points and decreased levels at 24 and 48 hours after treatment. c-Jun increased as early as 6 hours after treatment and returned to lower (yet still elevated over control) levels by 48 hours. To determine possible functional consequences of increased c-Jun expression, gel electrophoretic mobility assays were conducted that showed increased AP-1 binding at 24 and 48 hours after treatment. These data show that VES induces apoptosis in reticuloendotheliosis virus-transformed lymphoid cells and suggest that decreases of c-Myc protein and increases of c-Jun protein and DNA binding capacity may be playing a role in VES-mediated events leading to apoptosis in this cell type.

Authors+Show Affiliations

Genetics Institute, University of Texas at Austin 78712-1097, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8837858

Citation

Qian, M, et al. "RRR-alpha-tocopheryl Succinate Induces Apoptosis in Avian Retrovirus-transformed Lymphoid Cells." Nutrition and Cancer, vol. 25, no. 1, 1996, pp. 9-26.
Qian M, Sanders BG, Kline K. RRR-alpha-tocopheryl succinate induces apoptosis in avian retrovirus-transformed lymphoid cells. Nutr Cancer. 1996;25(1):9-26.
Qian, M., Sanders, B. G., & Kline, K. (1996). RRR-alpha-tocopheryl succinate induces apoptosis in avian retrovirus-transformed lymphoid cells. Nutrition and Cancer, 25(1), 9-26.
Qian M, Sanders BG, Kline K. RRR-alpha-tocopheryl Succinate Induces Apoptosis in Avian Retrovirus-transformed Lymphoid Cells. Nutr Cancer. 1996;25(1):9-26. PubMed PMID: 8837858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RRR-alpha-tocopheryl succinate induces apoptosis in avian retrovirus-transformed lymphoid cells. AU - Qian,M, AU - Sanders,B G, AU - Kline,K, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 9 EP - 26 JF - Nutrition and cancer JO - Nutr Cancer VL - 25 IS - 1 N2 - The RRR-alpha-tocopheryl succinate form of vitamin E [vitamin E succinate (VES)] inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner, blocks the cells in the G2/M cell cycle phase, and induces the cells to undergo apoptosis. Apoptosis was documented by demonstrating changes that are characteristic of this type of cell death, including morphological analyses of chromatin condensation by 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining using scanning confocal and traditional fluorescent microscopy; flow cytometry analyses of propidium iodide-labeled DNA showing fragmented DNA as a pre-G1 peak; two-color flow cytometry analyses of intact cells labeled first by the TUNEL procedure (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeled DNA stained with fluorescein isothiocyanate-labeled avidin) and then by propidium iodide demonstrating fragmented DNA; and electrophoresis of DNA showing a DNA ladder created by internucleosomal DNA fragmentation. The percentage of apoptotic cells was determined by DAPI staining and showed 11%, 27%, and 49% of cells to be apoptotic after treatment with 10 micrograms/ml VES for one, two, and three days, respectively. Analyses of mRNA levels of genes that have been implicated in the apoptotic process, namely, bcl-2, c-myc, and c-jun, revealed no change in bcl-2, decreases in c-myc mRNA levels after 36 hours of treatment, and increases in c-jun mRNA levels within four hours after treatment. Western immunoblotting analyses of protein levels for the transcription factors c-Myc and c-Jun showed normal levels of c-Myc at early time points and decreased levels at 24 and 48 hours after treatment. c-Jun increased as early as 6 hours after treatment and returned to lower (yet still elevated over control) levels by 48 hours. To determine possible functional consequences of increased c-Jun expression, gel electrophoretic mobility assays were conducted that showed increased AP-1 binding at 24 and 48 hours after treatment. These data show that VES induces apoptosis in reticuloendotheliosis virus-transformed lymphoid cells and suggest that decreases of c-Myc protein and increases of c-Jun protein and DNA binding capacity may be playing a role in VES-mediated events leading to apoptosis in this cell type. SN - 0163-5581 UR - https://www.unboundmedicine.com/medline/citation/8837858/RRR_alpha_tocopheryl_succinate_induces_apoptosis_in_avian_retrovirus_transformed_lymphoid_cells_ DB - PRIME DP - Unbound Medicine ER -