Dithiothreitol enhanced arsenic-trioxide-induced cell apoptosis in cultured oral cancer cells via mitochondrial dysfunction and endoplasmic reticulum stress.

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  • Additional Information
    • Source:
      Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 100885357 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-7278 (Electronic) Linking ISSN: 15204081 NLM ISO Abbreviation: Environ Toxicol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : John Wiley & Sons, c1999-
    • Subject Terms:
      Antineoplastic Agents/*toxicity ; Apoptosis/*drug effects ; Dithiothreitol/*pharmacology ; Endoplasmic Reticulum Stress/*drug effects ; Mitochondrial Diseases/*chemically induced ; Mouth Neoplasms/*drug therapy ; Oxides/*toxicity ; Sulfhydryl Reagents/*pharmacology; Arsenic Trioxide ; Arsenicals ; Cell Line, Tumor ; Cell Survival/drug effects ; Comet Assay ; DNA Damage ; Drug Synergism ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondrial Diseases/metabolism ; Mitochondrial Diseases/pathology ; Mouth Neoplasms/pathology
    • Abstract:
      Arsenic is naturally occurring toxic metalloid and drinking As 2 O 3 containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease, hypertension, and cancer. On the contrary, As 2 O 3 has been an ancient drug used in traditional Chinese medicine with substantial anticancer activities, especially in the treatment of acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As 2 O 3 action in solid cancer cells, such as oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of tumor and nontumor cells from the oral cancer patients and treated the cells with As 2 O 3 alone or combined with dithiothreitol (DTT). The results showed that 0.5 μM As 2 O 3 plus 20 μM DTT caused a significant cell death of oral cancer cells but not the nontumor cells. Also As 2 O 3 plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in oral cancer cells. On the other way, As 2 O 3 also triggered endoplasmic reticulum stress and increased the levels of glucose-regulated protein 78, calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As 2 O 3 on killing oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in oral cancer therapy and worth further investigations. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 17-27, 2017.
      (© 2015 Wiley Periodicals, Inc.)
    • Contributed Indexing:
      Keywords: apoptosis; arsenic trioxide; dithiothreitol; endoplasmic reticulum stress; oral cancer; traditional Chinese medicine
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Arsenicals)
      0 (Oxides)
      0 (Sulfhydryl Reagents)
      S7V92P67HO (Arsenic Trioxide)
      T8ID5YZU6Y (Dithiothreitol)
    • Publication Date:
      Date Created: 20151024 Date Completed: 20170302 Latest Revision: 20181202
    • Publication Date:
      20231215
    • Accession Number:
      10.1002/tox.22208
    • Accession Number:
      26494474