DMC is not better than TMZ on intracranial anti-glioma effects

J Cell Biochem. 2018 Jul;119(7):6057-6064. doi: 10.1002/jcb.26803. Epub 2018 Mar 25.

Abstract

Previous studies showed Demethoxycurcumin (DMC) has stronger anti-glioma and anti-GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower toxicity than TMZ on nude mice. However, this conclusion was confirmed to be wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected with U87MG-luc cells in the caudate nucleus of the brain and treated with DMC (30 mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection. Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Western blot was used to detect the expression of p-Akt, cleaved-caspase-3 and Bax. The average value of BLI showed TMZ determined a significant tumor regression while DMC had a mild regression effect on tumor growth compared with control group. Immunohistochemistry for Ki67, proliferating cell nuclear antigen (PCNA), and TUNEL demonstrated that TMZ more effectively inhibited the expression of Ki67 and PCNA, and increased the ratio of TUNEL-positive cells in in situ tumor tissue. Western blot analysis also indicated that TMZ but not DMC more significantly decreased p-Akt and increased cleaved-caspase-3 and Bax expression.These findings suggested a fact that TMZ appear to be more effective in controlling the growth of glioblastoma than DMC in an orthotopic glioblastoma xenograft model.

Keywords: apoptosis; demethoxycurcumin; glioblastoma; proliferation; temozolomide.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacology
  • Diarylheptanoids
  • Glioma / drug therapy
  • Glioma / pathology*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Temozolomide / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Alkylating
  • Diarylheptanoids
  • Curcumin
  • demethoxycurcumin
  • Temozolomide