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Tetramethylpiperidine-Substituted Phenazines Inhibit the Proliferation of Intrinsically Multidrug Resistant Carcinoma Cell Lines

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Abstract

The effects of nine newtetramethylpiperidine (TMP)-substitutedphenazines on the growth of a humanesophageal cancer cell line (WHCO3),two human hepatocellular carcinoma celllines (PLC and HepG2) and three human coloncancer cell lines (CaCo2, COLO 320DMand HT29) were compared to those ofclofazimine, B669 and five standardchemotherapeutic agents. The three mostactive TMP-substituted phenazines againstthese cell lines were B3962, B4126 andB4125 with mean IC50 values for allthe cancer cell lines tested of 0.36, 0.47and 0.48 μg/ml respectively. B3962 andB4126, but not B4125 were also the mostactive against a semi-continuous humanfibroblast culture (MRC5). The compoundwith the highest tumor specificity relativeto the fibroblast culture, was B4125. Importantly, there was minimal variation insensitivity of the different cell lines,including a multidrug resistant cell line(COLO 320DM) expressing high levels ofP-glycoprotein, to the TMP-substitutedphenazines. This was not the case with thestandard chemotherapeutic agents. Theefficacy of compounds such as B4125 againsta broad spectrum of multidrug resistantcancer cell lines, together with theirrelatively high tumor specificity, suggeststhat these agents may be useful in thetreatment of intrinsically resistantcancers such as colon and liver cancer.

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Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, University of Pretoria, Pretoria, South Africa

    Esme van Niekerk

  2. Department of Chemistry, University College Dublin, Belfield, Republic of Ireland

    John F. O'Sullivan

  3. Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, Pretoria, South Africa

    Gisela K. Jooné & Constance E.J. van Rensburg

Authors
  1. Esme van Niekerk
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  2. John F. O'Sullivan
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  3. Gisela K. Jooné
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  4. Constance E.J. van Rensburg
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van Niekerk, E., O'Sullivan, J.F., Jooné, G.K. et al. Tetramethylpiperidine-Substituted Phenazines Inhibit the Proliferation of Intrinsically Multidrug Resistant Carcinoma Cell Lines. Invest New Drugs 19, 211–217 (2001). https://doi.org/10.1023/A:1010691714635

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