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Tetrandrine enhances the anticancer effects of arsenic trioxide in vitro.

Abstract
Arsenic trioxide (As2O3), an effective agent to treat leukemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden death have been implicated in the cardiotoxicity of As2O3. The present study was designed to assess whether the combination of As2O3 and tetrandrine could generate a more powerful anti-cancer effect. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed for detecting the proliferation of HepG2 and A549 cells treated with tetrandrine and As2O3. Fluorescent microscopy measurements and flow cytometry were carried out to evaluate the apoptosis in HepG2 cells. The cell cycle arrest of HepG2 cells was also determined by flow cytometry. The cell proliferation assay in HepG2 and A549 cells indicated that tetrandrine significantly enhanced the inhibit effect of As2O3. In addition, the following Isobolograms further demonstrated that combining As2O3 with tetrandrine generated synergism action. Tetrandrine also enhanced the apoptosis, necrosis and cell cycle arrest in As2O3-treated HepG2 cells. Our present study showed that tetrandrine can dramatically enhance the anti- cancer effect induced by As2O3. Combining As2O3 with tetrandrine would be a novel strategy to treat cancer in clinical practice.
AuthorsYouran Chen, Peichun Li, Shen Yang, Nannan Tong, Jie Zhang, Xiaoyan Zhao
JournalInternational journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 52 Issue 5 Pg. 416-24 (May 2014) ISSN: 0946-1965 [Print] Germany
PMID24548979 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Arsenicals
  • Benzylisoquinolines
  • Oxides
  • tetrandrine
  • Arsenic Trioxide
Topics
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology)
  • Apoptosis (drug effects)
  • Arsenic Trioxide
  • Arsenicals (pharmacology)
  • Benzylisoquinolines (pharmacology)
  • Cell Cycle Checkpoints (drug effects)
  • Cell Proliferation (drug effects)
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Necrosis
  • Neoplasms (pathology)
  • Oxides (pharmacology)
  • Time Factors

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