4.6 Article

Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1-1 inhibitor, in tumorigenesis and tumor progression

Journal

JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 120, Issue 5, Pages 7045-7055

Publisher

WILEY
DOI: 10.1002/jcb.27974

Keywords

adjuvant therapy; breast cancer; chlorophyllin; GST P1-1 inhibitor

Funding

  1. Teaching Staff Training Program
  2. Hacettepe University Scientific Research Unit [012 D09 101 001-20]
  3. TUBITAK (The Scientific and Technological Research Council of Turkey) [109S362]

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Glutathione (GSH) and enzymes related to this antioxidant molecule are often overexpressed in tumor cells and may contribute to drug resistance. Blockade of glutathione transferases (GSTs) has been proposed to potentiate the efficacy of chemotherapeutic drugs in cancer. The aim of this study was to evaluate the effect of chlorophyllin that has antioxidant properties, and also interferes with the activity of GST P1-1, on breast cancers in vitro and in vivo. The in vivo studies were conducted using an N-methyl-N-nitrosourea (MNU)-induced chemical carcinogenesis model in laboratory rats. DNA damage, GST activity, and GSH levels were determined in liver and tumor tissues. Treatment with chlorophyllin increased the GSH levels in the liver and significantly decreased DNA damage in the blood, liver, and tumor tissues. Even though tumorigenesis was delayed in rats receiving chlorophyllin before MNU injections, once the tumors emerged, the progression of tumor appeared to be faster than in the animals that received the carcinogen only. Out of nine breast cell lines, GST P1-1 expression was detected in MCF-12A, MDA-MB-231, and HCC38. Concomitant incubation with chlorophyllin and docetaxel did not significantly affect cell proliferation and viability. Chlorophyllin displayed genoprotective effects that initially delayed tumorigenesis. However, once the tumors were established, it may act as a promoter that facilitates tumor growth, potentially by a mechanism independent of cell proliferation and viability. Our results underline the pros and cons of antioxidant treatment in cancer, even if it has a capacity to inhibit GST P1-1.

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