Antitumor activity of 3,5,4′-trimethoxystilbene in COLO 205 cells and xenografts in SCID mice

Min Hsiung Pan, Jia Hui Gao, Ching Shu Lai, Ying Jan Wang, Wen Ming Chen, Chih Yu Lo, Mingfu Wang, Slavik Dushenkov, Chi Tang Ho

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. Here we report that 3,5,4′-thmethoxystilbene (MR-3), the permethylated derivative of R-3 was more potent against the growth of human cancer cells (HT-29, PC-3, COLO 205) with estimated IC50 values of 81.31,42.71, and 6.25 μM, respectively. We further observed that MR-3 induced apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of MR-3-induced apoptosis, preceding cytochrome-c release, caspase activation, and DNA fragmentation. Significant therapeutic effects were demonstrated in vivo by treating severe combined immune deficiency (SCID) mice bearing COLO 205 tumor xenografts with MR-3 (50 mg/kg ip). Assays on DNA fragmentation and caspase activation were performed and demonstrated that apoptosis occurred in tumor tissues treated with MR-3. The appearance of apoptotic cells, as shown by Hematoxylin and Eosin (H&E) staining, and an increase in p21 and decrease in proliferating cell nuclear antigen (PCNA) protein by immuno-histochemistry were observed in tumor tissues under MR-3 treatment. Our study identifies the novel mechanisms of the antitumor effects of MR-3 and indicates that these results may have significant applications for cancer chemotherapy.

Original languageEnglish (US)
Pages (from-to)184-196
Number of pages13
JournalMolecular Carcinogenesis
Volume47
Issue number3
DOIs
StatePublished - Mar 1 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Keywords

  • Apoptosis
  • Caspase-3
  • Caspase-9
  • Cytochrome-c
  • MR-3
  • SCID mice
  • p53

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