Dimeric naphthoquinones, a novel class of compounds with prostate cancer cytotoxicity

Ashley E. Ross, Ashkan Emadi, Luigi Marchionni, Paula Hurley, Brian W. Simons, Edward M. Schaeffer, Milena Vuica-Ross

Research output: Contribution to journalArticle

Abstract

OBJECTIVES To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells. To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel. MATERIALS AND METHODS The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen-independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs). BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action. Synergistic effects with radiation and docetaxel were explored using colony-forming and MTT assays. RESULTS At concentrations of 15μM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines. Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays. Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis. BiQ cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity in PrECs, PC-3 and 22RV1, but not DU-145 cells. Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC50s of these compounds in PrECs. Co-administration of BiQs with docetaxel had minimal additive effects. CONCLUSIONS Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction. Further studies are warranted to better characterize this class of potential chemo-therapeutics.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalBJU International
Volume108
Issue number3
DOIs
StatePublished - Aug 2011

Fingerprint

Naphthoquinones
docetaxel
Prostatic Neoplasms
Prostate
Epithelial Cells
Radiation Effects
Androgens
Reactive Oxygen Species
Cell Line
Cytotoxins
NADP
Oxidoreductases
Radiotherapy
Therapeutics
Adenosine Triphosphate
Radiation
Apoptosis

Keywords

  • cytotoxicity
  • dimeric naphthoquinones
  • oxidative stress
  • prostate cancer
  • radiation synergy

ASJC Scopus subject areas

  • Urology

Cite this

Dimeric naphthoquinones, a novel class of compounds with prostate cancer cytotoxicity. / Ross, Ashley E.; Emadi, Ashkan; Marchionni, Luigi; Hurley, Paula; Simons, Brian W.; Schaeffer, Edward M.; Vuica-Ross, Milena.

In: BJU International, Vol. 108, No. 3, 08.2011, p. 447-454.

Research output: Contribution to journalArticle

Ross, Ashley E. ; Emadi, Ashkan ; Marchionni, Luigi ; Hurley, Paula ; Simons, Brian W. ; Schaeffer, Edward M. ; Vuica-Ross, Milena. / Dimeric naphthoquinones, a novel class of compounds with prostate cancer cytotoxicity. In: BJU International. 2011 ; Vol. 108, No. 3. pp. 447-454.
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abstract = "OBJECTIVES To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells. To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel. MATERIALS AND METHODS The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen-independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs). BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action. Synergistic effects with radiation and docetaxel were explored using colony-forming and MTT assays. RESULTS At concentrations of 15μM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines. Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays. Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis. BiQ cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity in PrECs, PC-3 and 22RV1, but not DU-145 cells. Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC50s of these compounds in PrECs. Co-administration of BiQs with docetaxel had minimal additive effects. CONCLUSIONS Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction. Further studies are warranted to better characterize this class of potential chemo-therapeutics.",
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AU - Ross, Ashley E.

AU - Emadi, Ashkan

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AU - Schaeffer, Edward M.

AU - Vuica-Ross, Milena

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N2 - OBJECTIVES To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells. To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel. MATERIALS AND METHODS The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen-independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs). BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action. Synergistic effects with radiation and docetaxel were explored using colony-forming and MTT assays. RESULTS At concentrations of 15μM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines. Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays. Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis. BiQ cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity in PrECs, PC-3 and 22RV1, but not DU-145 cells. Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC50s of these compounds in PrECs. Co-administration of BiQs with docetaxel had minimal additive effects. CONCLUSIONS Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction. Further studies are warranted to better characterize this class of potential chemo-therapeutics.

AB - OBJECTIVES To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells. To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel. MATERIALS AND METHODS The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen-independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs). BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action. Synergistic effects with radiation and docetaxel were explored using colony-forming and MTT assays. RESULTS At concentrations of 15μM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines. Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays. Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis. BiQ cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity in PrECs, PC-3 and 22RV1, but not DU-145 cells. Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC50s of these compounds in PrECs. Co-administration of BiQs with docetaxel had minimal additive effects. CONCLUSIONS Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction. Further studies are warranted to better characterize this class of potential chemo-therapeutics.

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