Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β-lapachone in melanoma cell lines

NAD(P)H quinone oxidoreductase 1 (NQO1)-dependent antitumor drugs such as β-lapachone (β-lap) are attractive candidates for cancer chemotherapy because several tumors exhibit higher expression of NQO1 than adjacent tissues. Although the association between NQO1 and β-lap has been elucidated, the eff...

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Bibliographic Details
Published in:Oncology letters 2018-02, Vol.15 (2), p.2393-2400
Main Authors: Arakawa, Nobuyuki, Okubo, Ayaka, Yasuhira, Shinji, Takahashi, Kazuhiro, Amano, Hiroo, Akasaka, Toshihide, Masuda, Tomoyuki, Shibazaki, Masahiko, Maesawa, Chihaya
Format: Article
Language:English
Subjects:
Acids
Chemotherapy
Kinases
Melanoma
Mutation
Oncology
Penicillin
Skin cancer
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Summary:NAD(P)H quinone oxidoreductase 1 (NQO1)-dependent antitumor drugs such as β-lapachone (β-lap) are attractive candidates for cancer chemotherapy because several tumors exhibit higher expression of NQO1 than adjacent tissues. Although the association between NQO1 and β-lap has been elucidated, the effects of a NQO1-inducer and β-lap used in combination remain to be clarified. It has previously been reported that melanoma cell lines have detectable levels of NQO1 expression and are sensitive to NQO1-dependent drugs such as 17-allylamino-17-demethoxygeldanamycin. The present study was conducted to investigate the involvement of NQO1 in β-lap-mediated toxicity and the utility of combination treatment with a NQO1-inducer and β-lap in malignant melanoma cell lines. Decreased expression or inhibition of NQO1 caused these cell lines to become less sensitive to β-lap, indicating a requirement of NQO1 activity for β-lap-mediated toxicity. Of note was that carnosic acid (CA), a compound extracted from rosemary, was able to induce further expression of NQO1 through NF-E2 related factor 2 (NRF2) stabilization, thus significantly enhancing the cytotoxicity of β-lap in all of the melanoma cell lines tested. Taken together, the data presented in the current study indicated that the NRF2-NQO1 axis may have potential value as a therapeutic target in malignant melanoma to improve the rate of clinical response to NQO1-dependent antitumor drugs.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2017.7618