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

  • Authors:
    • Nobuyuki Arakawa
    • Ayaka Okubo
    • Shinji Yasuhira
    • Kazuhiro Takahashi
    • Hiroo Amano
    • Toshihide Akasaka
    • Tomoyuki Masuda
    • Masahiko Shibazaki
    • Chihaya Maesawa
  • View Affiliations

  • Published online on: December 14, 2017     https://doi.org/10.3892/ol.2017.7618
  • Pages:2393-2400
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Abstract

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.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Arakawa, N., Okubo, A., Yasuhira, S., Takahashi, K., Amano, H., Akasaka, T. ... Maesawa, C. (2018). Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines. Oncology Letters, 15, 2393-2400. https://doi.org/10.3892/ol.2017.7618
MLA
Arakawa, N., Okubo, A., Yasuhira, S., Takahashi, K., Amano, H., Akasaka, T., Masuda, T., Shibazaki, M., Maesawa, C."Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines". Oncology Letters 15.2 (2018): 2393-2400.
Chicago
Arakawa, N., Okubo, A., Yasuhira, S., Takahashi, K., Amano, H., Akasaka, T., Masuda, T., Shibazaki, M., Maesawa, C."Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines". Oncology Letters 15, no. 2 (2018): 2393-2400. https://doi.org/10.3892/ol.2017.7618