Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of β-Lapachone

Park, Heon Joo; Choi, Eun Kyung; Choi, Ji-Hyung; Ahn, Ki Jung; Kim, Eun Jung; Ji, In Mi; Kook, Yeon Hee; Ahn, Seung Do; Williams, Brent; Griffin, Robert J.; Boothman, David A.; Lee, Chung K.; Song, Chang W.

doi:10.1158/1078-0432.ccr-05-0818

Cited by 38 publications

(53 citation statements)

References 35 publications

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“…The transfected cells were further incubated with 1,000 μg/ml G418 for 7 days and a single colony of nqo1 knock-down A549 cells (shNQO1 A549) was amplified (Pink et al, 2000;Park et al, 2005b).…”

Section: Nqo1 Shrna Transfectionmentioning

confidence: 99%

“…A549 cells grown in flasks were washed twice with ice-cold PBS, scraped from the dishes and lysed with RIPA buffer (Park et al, 2005b;Suzuki et al, 2006;Choi et al, 2007). The lysates were centrifuged, and an equal amount of protein from each sample was resolved using an 8 to 10% SDS-polyacrylamide gel electrophoresis and transferring to a Hybond-P (Amersham Life Sciences) membrane.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…In addition to killing a variety of cancer cells, β-lap has been shown to sensitize cancer cells to radiation by inhibiting the repair of sublethal radiation damage (Boothman et al, 1993;Park et al, 2005b;Suzuki et al, 2006;Choi et al, 2007). The anti-tumor activity and the radiosensitizing activity of β-lap are dependent on the cytosolic flavoenzyme NAD(P)H:quinone oxidoreductase (NQO1, E＞C＞1.6.99.2), which catalyzes the two-electron reduction of endogenous as well as exogenous quinone compounds to their corresponding hydroquinone forms using H + from NADH or NADPH (Boothman et al, 1993;Trush et al, 1996;Pink et al, 2000;Planchon et al, 2001;Tagliarino et al, 2001;Park et al, 2005aPark et al, , 2005bSuzuki et al, 2006;Bey et al, 2007;Choi et al, 2007;Song et al, 2008). Boothman and his colleagues (Trush et al, 1996;Pink et al, 2000;Planchon et al, 2001;Tagliarino et al, 2001;Park et al, 2005b;Bentle et al, 2006;Bey et al, 2007) proposed that NQO1 mediates the two-electron reduction of β-lap and that the reduced form of β-lap is unstable and thus immediately oxidized to the original oxidized form.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the futile cycling between the oxidized and reduced forms of β-lap causes depletion of ATP, the elevation of cytosolic Ca 2+ and the release of cytochrome C, thereby inducing cell death. Treatment of cells with dicoumarol, an inhibitor of NQO1 (Boothman et al, 1993;Park et al, 2005b;Suzuki et al, 2006; Song et al, 2008), or with the small interfering RNA (siRNA)-NQO1 (Choi et al, 2007) have been shown to effectively suppress the cytotoxic and radiosensitizing effects of β-lap. Furthermore, NQO1-null-cells were resistant to β-lap and this resistance could be reversed by administration of exogenous NQO1 (Pink et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the NQO1 content in various human cancer cells is significantly greater than that observed in normal tissues implying that tumors may be preferentially damaged by β-lap. Furthermore, NQO1 expression in cancer cells can be increased by a number of different types of stresses such as ionizing radiation (Choi et al, 2007), heat shock (Park et al, 2005b) and certain chemotherapeutic drugs such as cisplatin (Terai et al, 2009). These observations strongly indicated that conventional cancer treatments may increase the sensitivity of the cancer to β-lap treatment by increasing NQO1 activity in the target tumor cells (Park et al, 2005b;Suzuki et al, 2006;Choi et al, 2007;Song et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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β-Lapachone suppresses radiation-induced activation of nuclear factor-κB

Dong

Lee

et al. 2010

Exp Mol Med

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Anticancer effects of β-lapachone (β-lap) are due to generation of ROS and metabolic catastrophes as a result of NAD(P)H:quinone oxidoreductase (NQO1)-mediated futile cycling between the oxidized and reduced forms of β-lap. It has been shown that NQO1 is also essential for the TNF-induced activation of NF-κB and that β-lap suppresses the TNF-induced NF-κB activation. We investigated whether or not NQO1 is involved and β-lap suppresses the radiation-induced NF-κB activation using A549 human lung cancer cells and NQO1-knock down A549 cells (shNQO1 A549 cells). Irradiation with 4 Gy markedly increased the DNA binding activity of NF-κB in A549 cells, but not in the shNQO1 A549 cells, thus demonstrating that NQO1 plays a pivotal role in irradiation-induced NF-κB activation. Treatment with 10 μM β-lap for 4 h almost completely abrogated the radiation-induced increase in NF-κB activation and the transcription of NF-κB target genes such as bcl2, gadd45β and cyclinD1. Moreover, β-lap markedly suppressed the activation of IκB kinase γ (IKKγ) and the subsequent phosphorylation of IκBα, thereby inhibiting NF-κB activation. It is concluded that β-lap suppresses the radiation-induced activation of NF-κB by interrupting the involvement of NQO1 in the activation of NF-κB, thereby inhibiting the transcription of survival signals. The radiosensitization caused by β-lap may, in part, be attributed to β-lap-induced suppression of NF-κB activation.

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Section: Nqo1 Shrna Transfectionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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β-Lapachone suppresses radiation-induced activation of nuclear factor-κB

Dong

Lee

et al. 2010

Exp Mol Med

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Mornings with art, lessons learned: Feedback regulation, restriction threshold biology, and redundancy govern molecular stress responses

Bey

Wuerzberger-Davis

Pink

et al. 2006

Journal Cellular Physiology

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Work from the laboratory of Dr. Arthur B. Pardee has highlighted basic principles that govern cellular and molecular biological processes in living cells. Among the most important governing principles in cellular and molecular responses are: (i) threshold "restriction" responses, wherein a level of response is reached and a "point of no return" is achieved; (ii) feedback regulation; and (iii) redundancy. Lessons learned from the molecular biology of cellular stress responses in mammalian cancer versus normal cells after ionizing radiation (IR) or chemotherapeutic agent exposures reveal similar instances of these guiding principles in mammalian cells. Among these are the: (i) induction of cell death responses by beta-lapachone (beta-lap), a naphthoquinone anti-tumor agent that kills cancer cells via an NQO1 (i.e., X-ray-inducible protein-3, xip3)-dependent mechanism; (ii) induction of secretory clusterin (sCLU) in response to TGF-beta1 exposure, and the ability of induced sCLU protein to down-regulate TGF-beta1 signaling; and (iii) induction of DNA mismatch repair-dependent G(2) cell cycle checkpoint responses after exposure to alkylating agents. We have learned these lessons and now adopted strategies to exploit them for improved therapy. These examples will be discussed and compared to the pioneering findings of researchers in the Pardee laboratory over the years.

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Inhibition of DNA Repair System Activity

Takahashi

2016

Hyperthermic Oncology From Bench to Bedside

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Hyperthermia is a potent sensitizer for cell killing by ionizing radiation and DNA damaging chemotherapeutic agents. Heat mediates these effects because it causes protein denaturation, which strongly depresses DNA repair mechanisms that otherwise contribute to the development of radio-and chemo-resistance. Therefore, hyperthermic therapy has been utilized to augment traditional cancer treatments such as radiotherapy and chemotherapy. Recently research has provided insights into the molecular mechanisms involved in DNA repair pathways, i.e. DNA damage responses, base excision repair, DNA single strand break repair, non-homologous end joining repair, and homologous recombination repair, and their effect in responses to hyperthermia. In this chapter, the DNA repair pathways that are relevant in the clinical treatment of cancer are reviewed. The effects of heat on DNA repair and the sensitization of cells to ionizing radiation and DNA damaging agents are also considered. This chapter is intended to provide an overview of the relationship between heat sensitivity and DNA repair.

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Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of β-Lapachone

Cited by 38 publications

References 35 publications

β-Lapachone suppresses radiation-induced activation of nuclear factor-κB

β-Lapachone suppresses radiation-induced activation of nuclear factor-κB

Mornings with art, lessons learned: Feedback regulation, restriction threshold biology, and redundancy govern molecular stress responses

Inhibition of DNA Repair System Activity

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