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Involvement of PKC in TPA-potentiated apoptosis induction during hemin-mediated erythroid differentiation in K562 cells

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Abstract

Triggering differentiation has been employed as a strategy to inhibit cell proliferation and accelerate apoptosis in malignant cells. To better understand the mechanisms underlying differentiation-mediated regulation of apoptosis, we have studied the effects of PKC pathway with an activator of the protein kinase C, 12-O-tetradecanoylphorbol-13-acetate (TPA), during hemin-induced erythroid differentiation of K562 erythroleukemia cells. K562 cell line has been used as a model of common progenitor of erythroblasts and magakaryocytes and can be differentiated into erythroid and megakaryocytic lineages by hemin and TPA, respectively. TPA induced almost complete loss of proliferation during megakaryocytic differentiation in K562 cells. However, upon hemin-mediated erythroid differentiation, the growth rate was slightly decreased at the subtoxic concentrations. Cotreatment with TPA at the hemin-treated K562 cells produced a concentration-dependent increase in cell injuries with apoptotic changes and significantly diminished the erythroid phenotype. To better understand the events implicated, we have used the PKC inhibitors such as bisindolylmaleimide II, RO318220, and the PKCβ inhibitor. Our data showed that TPA-potentiated apoptosis in hemin-treated K562 cells was rescued by the application of the PKC inhibitors. Taken together, our results suggested the involvement of PKC in TPA-potentiated apoptosis induction during hemin-mediated erythroid differentiation in K562 cells.

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Authors and Affiliations

  1. Department and Graduate School of Biotechnology, Fooyin University, 151 Chin-Hsueh, Rd., Ta-Liao Hsiang, Kaohsiung Hsien, 831, Taiwan, Republic of China

    Chih Chung Chou & Chen Ya Hsu

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  1. Chih Chung Chou
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  2. Chen Ya Hsu
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Correspondence to Chen Ya Hsu.

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Chou, C.C., Hsu, C.Y. Involvement of PKC in TPA-potentiated apoptosis induction during hemin-mediated erythroid differentiation in K562 cells. Naunyn-Schmied Arch Pharmacol 379, 1–9 (2009). https://doi.org/10.1007/s00210-008-0347-y

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  • DOI: https://doi.org/10.1007/s00210-008-0347-y

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