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Cancer Therapy: Preclinical

Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear Factor-κB Pathway

Yvonne G. Lin, Ajaikumar B. Kunnumakkara, Asha Nair, William M. Merritt, Liz Y. Han, Guillermo N. Armaiz-Pena, Aparna A. Kamat, Whitney A. Spannuth, David M. Gershenson, Susan K. Lutgendorf, Bharat B. Aggarwal and Anil K. Sood
Yvonne G. Lin
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Ajaikumar B. Kunnumakkara
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Asha Nair
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William M. Merritt
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Liz Y. Han
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Guillermo N. Armaiz-Pena
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Aparna A. Kamat
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Whitney A. Spannuth
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David M. Gershenson
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Susan K. Lutgendorf
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Bharat B. Aggarwal
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Anil K. Sood
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DOI: 10.1158/1078-0432.CCR-06-3072 Published June 2007
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    Fig. 1.

    A, cytotoxicity [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] graphs depicting the inhibitory concentration at 50% for SKOV3ip1 and HeyA8 cell lines in vitro. Varying doses of curcumin were given to HeyA8 and SKOV3ip1 cells (2,000 in 0.1 mL) for 72 h. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. B, apoptosis induction by docetaxel with (black columns) and without (white columns) curcumin in SKOV3ip1 and HeyA8 cells. Cells were coincubated with medium or the IC50 dose of curcumin (10 μmol/L) and varying doses of docetaxel. C, EMSA shows curcumin-mediated inhibition of TNF-α–induced (0.1 nmol/L for 30 min) NF-κB activation. Cells were treated with 10 μmol/L curcumin for 3, 6, 12, 24, 48, and 72 h.

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    Fig. 2.

    A, effect of curcumin on transcription factors NF-κB and activated STAT3 as examined by immunohistochemistry. Magnification, ×200. Maximal down-regulation of these transcription factors is seen by 24 h after exposure to curcumin (500 mg/kg). Expression of NF-κB and STAT3 is back to baseline by 72 h after exposure. B, effect of curcumin on VEGF, IL-8, and MMP-9 as examined by immunohistochemistry. Magnification, ×100. C, effect of curcumin on COX-2 as seen on immunohistochemistry. Magnification, ×200.

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    Fig. 3.

    Mean tumor weights and distribution from curcumin therapy experiments. Mice inoculated with SKOV3ip1 (A), HeyA8 (B), and HeyA8-MDR (C) received either vehicle alone (control), curcumin alone (500 mg/kg), docetaxel alone (35 or 50 μg once weekly depending on cell line), or combination curcumin plus docetaxel. Animals from all groups were sacrificed when control animals were moribund (approximately 3-4 weeks after initiating therapy depending on the cell line used). All tumors were harvested; the tumor weight and number of nodules were recorded. Columns, mean tumor weights for each sample group; bars, SE. *, P ≤ 0.05; †, P ≤ 0.01; ‡, P ≤ 0.001.

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    Fig. 4.

    A, proliferative index for SKOV3ip1 tumors with representative PCNA immunohistochemical sections from tumors collected at necropsy. B, box plot of MVD for SKOV3ip1 tumors with representative CD31 immunohistochemical sections from tumors collected at necropsy. ○, outliers. *, P ≤ 0.01; †, P ≤ 0.001.

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    Effect of curcumin-based therapy on ovarian cancer growth

    Cell lineTreatmentMedian no. nodules (range)P (vs control)
    SKOV3ip1Control24 (2-32)
    Curcumin4.5 (1-26)0.048
    Docetaxel3 (2-5)0.01
    Curcumin + docetaxel1.5 (1-5)<0.001
    HeyA8Control4 (1-6)
    Curcumin3 (1-12)NS
    Docetaxel1.5 (1-5)0.01
    Curcumin + docetaxel1.5 (1-15)0.06
    HeyA8-MDRControl4 (1-11)
    Curcumin3 (1-11)NS
    Docetaxel9 (2-17)0.02
    Curcumin + docetaxel3 (1-10)0.06
    • Abbreviation: NS, not significant.

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Clinical Cancer Research: 13 (11)
June 2007
Volume 13, Issue 11
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Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear Factor-κB Pathway
Yvonne G. Lin, Ajaikumar B. Kunnumakkara, Asha Nair, William M. Merritt, Liz Y. Han, Guillermo N. Armaiz-Pena, Aparna A. Kamat, Whitney A. Spannuth, David M. Gershenson, Susan K. Lutgendorf, Bharat B. Aggarwal and Anil K. Sood
Clin Cancer Res June 1 2007 (13) (11) 3423-3430; DOI: 10.1158/1078-0432.CCR-06-3072

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Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear Factor-κB Pathway
Yvonne G. Lin, Ajaikumar B. Kunnumakkara, Asha Nair, William M. Merritt, Liz Y. Han, Guillermo N. Armaiz-Pena, Aparna A. Kamat, Whitney A. Spannuth, David M. Gershenson, Susan K. Lutgendorf, Bharat B. Aggarwal and Anil K. Sood
Clin Cancer Res June 1 2007 (13) (11) 3423-3430; DOI: 10.1158/1078-0432.CCR-06-3072
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