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 language | English (US) |
|---|---|
| Pages (from-to) | 95-102 |
| Number of pages | 8 |
| Journal | Cancer Biology and Therapy |
| Volume | 4 |
| Issue number | 1 |
| State | Published - Jan 2005 |
Fingerprint
Keywords
- B-lapachone
- Cyclodextrins
- NAD(P)H:quinone oxidoreductase
- Pancreatic cancer
- Quinones
- Reactive oxygen species
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Efficacy of β-lapachone in pancreatic cancer treatment
T2 - Exploiting the novel, therapeutic target NQO1
AU - Ough, Matthew
AU - Lewis, Anne
AU - Bey, Erik A.
AU - Gao, Jinming
AU - Ritchie, Justine M.
AU - Bornmann, William
AU - Boothman, David A.
AU - Oberley, Larry W.
AU - Cullen, Joseph J.
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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.
KW - B-lapachone
KW - Cyclodextrins
KW - NAD(P)H:quinone oxidoreductase
KW - Pancreatic cancer
KW - Quinones
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=24644432026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24644432026&partnerID=8YFLogxK
M3 - Article
C2 - 15662131
AN - SCOPUS:24644432026
VL - 4
SP - 95
EP - 102
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
SN - 1538-4047
IS - 1
ER -