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Antitumor effects of KITC, a new resveratrol derivative, in AsPC-1 and BxPC-3 human pancreatic carcinoma cells

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Summary

Pancreatic cancer is a very aggressive malignant disease due to lack of early diagnosis and chemotherapeutic resistance of the tumor cells. There is distinct evidence that food derived polyphenols possess chemopreventive effects in the development of several cancers including pancreatic carcinoma. Resveratrol is one of those phenolic compounds found in grape skins and other fruits with known anticancer activity. Various polymethoxylated resveratrol derivatives showed stronger antiproliferative effects than resveratrol in tumor cell lines. The aim of our study was to evaluate the cytotoxic and biochemical effects of a newly synthesized polymethoxylated resveratrol analogue, N-hydroxy-N′-(3,4,5-trimethoxphenyl)-3,4,5-trimethoxy-benzamidine (KITC) in two human pancreatic cancer cell lines. The human pancreatic cancer cell lines, AsPC-1 and BxPC-3 were used to test the potential inhibitory effect of the resveratrol derivative on cell proliferation and the underlying mechanisms of this effect. After 7 days of incubation, KITC inhibited the growth of AsPC-1 and BxPC-3 cells with IC50 values of 9.6 and 8.7 μM, respectively. KITC (40 μM) arrested cells in the G0/G1 phase and depleted cells in the S phase of the cell cycle (−105% and −35% of control, respectively). KITC induced dose-dependent apoptosis in both pancreatic cancer cell lines and was found to significantly reduce the in situ activity of ribonucleotide reductase, the key enzyme of DNA synthesis. Employing growth inhibition assays, KITC acted synergistically with gemcitabine in both cell lines. In summary, we found that KITC exerted considerable antitumor activity against human pancreatic cancer cells and could be a promising candidate for further investigations to establish a new chemotherapeutic regimen.

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Authors and Affiliations

  1. Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria

    Astrid Bernhaus, Maria Ozsvar-Kozma, Philipp Saiko, Margit Jaschke, Monika Fritzer-Szekeres & Thomas Szekeres

  2. Division of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria

    Andreas Lackner & Michael Grusch

  3. Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria

    Zsuzsanna Horvath, Sibylle Madlener & Georg Krupitza

  4. Department of Medicinal Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria

    Norbert Handler & Thomas Erker

  5. Department of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria

    Walter Jaeger

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  1. Astrid Bernhaus
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  2. Maria Ozsvar-Kozma
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Bernhaus, A., Ozsvar-Kozma, M., Saiko, P. et al. Antitumor effects of KITC, a new resveratrol derivative, in AsPC-1 and BxPC-3 human pancreatic carcinoma cells. Invest New Drugs 27, 393–401 (2009). https://doi.org/10.1007/s10637-008-9183-7

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