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In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells

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Abstract

The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells. Apigenin (50% inhibition concentration, IC50 = 1.8 ± 0.5 μM) and diazepam (IC50 = 7.0 ± 0.5 μM) showed concentration-dependent inhibition of SNU-C4 cancer cell survival. Efficacy of cancer cell survival inhibition by apigenin and diazepam was much lower than that of 5-fluorouracil (5-FU), a known chemotherapeutic drug. However, 10−6 M concentration of apigenin and diazepam potentiated 5-FU-induced cytotoxicity. In SNU-C4 cells, 10−6 M concentrations of diazepam, flumazenil (Ro15-1788), Ro5-4864, or PK11195, all ligands for central- or peripheral-type benzodiazepine (BZD) receptors, inhibited cell survival like the flavonoid apigenin (4′,5,7-trihydroxyflavone) and fisetin (3,7,3′,4′-tetrahydroxyflavone). Also like the plant flavonoids, treatment with 10−6 M concentration of diazepam for 3 days hardly affect the peripheral-type BZD receptor (PBR) messenger RNA (mRNA) expression and inhibited glucose utilization of SNU-C4 cells. Treatment with flavonoids or diazepam for 6 days upregulated PBR mRNA expression and cell cytotoxicity of SNU-C4 cells. Furthermore, treatment with 10−6 M concentration of apigenin, a natural sedative material originating from traditional herbs, positively modulated BZD-induced antiproliferative cytotoxicity in SNU-C4 cells. Overall, the in vitro antiproliferative activity on SNU-C4 cancer cells of herbal sedatives, such as apigenin, plus additive enhancement of synthetic BZD- and 5-FU-induced antiproliferative activities, were shown. In conclusion, this study provides experimental basis for advanced trial in the future.

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Acknowledgments

This work was supported by BioMedical Research Institute grant, Kyungpook National University Hospital (2005).

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Authors and Affiliations

  1. Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 101, Dongin 2-Ga, Jung-Gu, Daegu, 700-422, Republic of Korea

    Sang-Woo Lee, Jae-Tae Lee, Sohn Joo Ahn, Yong Jin Lee, You La Lee, Jeongsoo Yoo & Byeong-Cheol Ahn

  2. Department of Pharmacology, School of Medicine, Kyungpook National University, 101, Dongin 2-Ga, Jung-Gu, Daegu, 700-422, Republic of Korea

    Maan-Gee Lee & Jeoung-Hee Ha

  3. Department of Neurology, School of Medicine, Kyungpook National University, 101, Dongin 2-Ga, Jung-Gu, Daegu, 700-422, Republic of Korea

    Ho Won Lee

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  1. Sang-Woo Lee
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Correspondence to Jeoung-Hee Ha.

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Lee, SW., Lee, JT., Lee, MG. et al. In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells. J Nat Med 63, 124–129 (2009). https://doi.org/10.1007/s11418-008-0300-x

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  • DOI: https://doi.org/10.1007/s11418-008-0300-x

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