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Resveratrol analog trans 3,4,5,4′-tetramethoxystilbene (DMU-212) mediates anti-tumor effects via mechanism different from that of resveratrol

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Abstract

Purpose

Resveratrol is a well-known chemopreventive and chemotherapeutic agent. Among all of the resveratrol analogs synthesized, 3,4,5,4′-tetramethoxystilbene (DMU-212) shows high activity and selectivity against various cancer cell types. The objective of this study is to investigate why DMU-212 has higher anti-tumor activity than resveratrol.

Methods

The effects of DMU-212 and resveratrol on cell viability, cell cycle, Stat3 activation, and microtubule dynamic were investigated and compared using MTT assay, cell cycle analysis, Western blot, tubulin polymerization assay, respectively, in MDA-MB-435 and MCF-7 human breast cancer cells.

Results

Compared to resveratrol, DMU-212 exerted a significantly higher growth inhibition in both cell lines. Further studies demonstrated that DMU-212 acted via different mechanisms from resveratrol. First, DMU-212 induced predominantly G2/M arrest whereas resveratrol induced G0/G1 arrest in both cell lines. Correlating with these findings, resveratrol induced more dramatic changes in the expression of Cyclin D1 compared to DMU-212. Second, DMU-212 induced apoptosis and reduced the expression of multiple anti-apoptotic proteins more appreciably than resveratrol. Third, while both agents inhibited Stat3 phosphorylation, treatments of DMU-212 but not resveratrol led to a significant increase in tubulin polymerization. The higher sensitivity to DMU-122 in MDA-MB-435 correlated with the more prominent effects seen in these parameters in this cell line, as compared to MCF7.

Conclusion

Compared to resveratrol, the novel stilbene derivative, DMU-212, had higher anti-tumor effects, which are likely owing to its modulation of multiple cellular targets.

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Acknowledgments

This work was supported through research grant from Canadian Institutes of Health Research (CIHR) (MOP 42407 and MOP 82884). We thank R × &D Health Research Foundation/CIHR for the Post-doctoral Fellowship in Pharmacy awarded to Zengshuan Ma. Natural Sciences and Engineering Research Council of Canada (NSERC) is also thanked for support (Dr Gossage RA).

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, 4119 Dentistry-Pharmacy Building, University of Alberta, Edmonton, AB, T6G 2N8, Canada

    Zengshuan Ma, Ommoleila Molavi, Azita Haddadi & Afsaneh Lavasanifar

  2. Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, AB, T6G 1Z2, Canada

    Raymond Lai

  3. Department of Chemistry, Acadia University, Wolfville, NS, B4P 2R6, Canada

    Robert A. Gossage

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  1. Zengshuan Ma
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  2. Ommoleila Molavi
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Correspondence to Afsaneh Lavasanifar.

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Ma, Z., Molavi, O., Haddadi, A. et al. Resveratrol analog trans 3,4,5,4′-tetramethoxystilbene (DMU-212) mediates anti-tumor effects via mechanism different from that of resveratrol. Cancer Chemother Pharmacol 63, 27–35 (2008). https://doi.org/10.1007/s00280-008-0704-z

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  • DOI: https://doi.org/10.1007/s00280-008-0704-z

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