Enhancement in alpha-tocopherol succinate-induced apoptosis by all-trans-retinoic acid in primary leukemic cells: role of antioxidant defense, Bax and c-myc.
We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by alpha-tocopherol succinate (alpha-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. alpha-TS at 50 microM concentration significantly decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) by 29% and 25%, respectively, and increased lipid peroxidation level by 33%. Though 10 microM ATRA did not affect these parameters, it further significantly enhanced alpha-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, alpha-TS, and their combination to 40%, 240%, and 320%, respectively, without any change in Bcl2 and p53 expression. C-myc was down regulated by treatment with ATRA, alpha-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of alpha-TS-induced apoptosis by ATRA in leukemic cells was through up regulation of Bax and lipid peroxidation, and down regulation of c-myc and GSH.
Khanduja
K L
KL
Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. klkhanduja@gmail.com
Kumar
S
S
Varma
N
N
Varma
S C
SC
Avti
P K
PK
Pathak
C M
CM
D000328:Adult; D000970:Antineoplastic Agents / Q000819:agonists / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000378:metabolism; D014212:Tretinoin / Q000819:agonists / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000819:agonists / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D000975:Antioxidants; C494826:BAX protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D014212:Tretinoin; D013482:Superoxide Dismutase; D005978:Glutathione; D024502:alpha-Tocopherol