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Enhancement in alpha-tocopherol succinate-induced apoptosis by all-trans-retinoic acid in primary leukemic cells: role of antioxidant defense, Bax and c-myc

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Abstract

We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by α-tocopherol succinate (α-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. α-TS at 50 μM 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 μM ATRA did not affect these parameters, it further significantly enhanced α-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, α-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, α-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of α-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.

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Authors and Affiliations

  1. Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    K. L. Khanduja, S. Kumar, P. K. Avti & C. M. Pathak

  2. Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    N. Varma

  3. Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    S. C. Varma

Authors
  1. K. L. Khanduja
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  2. S. Kumar
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  3. N. Varma
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  4. S. C. Varma
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  5. P. K. Avti
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  6. C. M. Pathak
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Correspondence to K. L. Khanduja.

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Khanduja, K.L., Kumar, S., Varma, N. et al. Enhancement in alpha-tocopherol succinate-induced apoptosis by all-trans-retinoic acid in primary leukemic cells: role of antioxidant defense, Bax and c-myc. Mol Cell Biochem 319, 133–139 (2008). https://doi.org/10.1007/s11010-008-9886-2

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  • DOI: https://doi.org/10.1007/s11010-008-9886-2

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