Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1

Matthew Ough, Anne Lewis, Erik A. Bey, Jinming Gao, Justine M. Ritchie, William Bornmann, David A. Boothman, Larry W. Oberley, Joseph J. Cullen

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

NAD(P)H:quinone oxidoreductase (NQO1) is elevated in human pancreatic cancers. We hypothesized that β-lapachone, a novel 1,2-naphthoquinone with potential antitumor activity in cancer cells expressing elevated levels of NQO1, would induce cytotoxicity in pancreatic cancer cells, wherein this two-electron reductase was recently found elevated, β-lapachone decreased clonogenic cell survival, metabolic cell viability, and anchorage-independent growth in soft agar. The cytotoxic in vitro effects of β-lapachone were inhibited with coadministration of dicumarol, a specific inhibitor of NQO1. In preestablished human pancreatic tumor xenografts in nude mice, β-lapachone demonstrated greater tumor growth inhibition when given intratumorally compared to when complexed with cyclodextrin to increase its bioavailability. Due to the poor prognosis of patients with pancreatic cancer and the limited effectiveness of surgery, chemotherapy, and radiation therapy, treatment regimens based on sound, tumor-specific rationales are desperately need for this disease.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalCancer Biology and Therapy
Volume4
Issue number1
StatePublished - Jan 2005

Fingerprint

Pancreatic Neoplasms
Neoplasms
Cell Survival
Oxidoreductases
Dicumarol
Cyclodextrins
Therapeutics
Growth
Heterografts
Nude Mice
NAD
Biological Availability
Agar
Radiotherapy
Electrons
Drug Therapy

Keywords

  • B-lapachone
  • Cyclodextrins
  • NAD(P)H:quinone oxidoreductase
  • Pancreatic cancer
  • Quinones
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ough, M., Lewis, A., Bey, E. A., Gao, J., Ritchie, J. M., Bornmann, W., ... Cullen, J. J. (2005). Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1. Cancer Biology and Therapy, 4(1), 95-102.

Efficacy of β-lapachone in pancreatic cancer treatment : Exploiting the novel, therapeutic target NQO1. / Ough, Matthew; Lewis, Anne; Bey, Erik A.; Gao, Jinming; Ritchie, Justine M.; Bornmann, William; Boothman, David A.; Oberley, Larry W.; Cullen, Joseph J.

In: Cancer Biology and Therapy, Vol. 4, No. 1, 01.2005, p. 95-102.

Research output: Contribution to journalArticle

Ough, M, Lewis, A, Bey, EA, Gao, J, Ritchie, JM, Bornmann, W, Boothman, DA, Oberley, LW & Cullen, JJ 2005, 'Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1', Cancer Biology and Therapy, vol. 4, no. 1, pp. 95-102.
Ough, Matthew ; Lewis, Anne ; Bey, Erik A. ; Gao, Jinming ; Ritchie, Justine M. ; Bornmann, William ; Boothman, David A. ; Oberley, Larry W. ; Cullen, Joseph J. / Efficacy of β-lapachone in pancreatic cancer treatment : Exploiting the novel, therapeutic target NQO1. In: Cancer Biology and Therapy. 2005 ; Vol. 4, No. 1. pp. 95-102.
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