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NQO1 induction mediated by photodynamic therapy synergizes with β-Lapachone-halogenated derivative against melanoma.

A new interesting article has been published in Biomed Pharmacother. 2018 Dec;108:1553-1564. doi: 10.1016/j.biopha.2018.09.159. Epub 2018 Oct 9. and titled:

NQO1 induction mediated by photodynamic therapy synergizes with β-Lapachone-halogenated derivative against melanoma.

Authors of this article are:

Lamberti MJ, Morales Vasconsuelo AB, Chiaramello M, Ferreira VF, Macedo Oliveira M, Baptista Ferreira S, Rivarola VA, Rumie Vittar NB.

A summary of the article is shown below:

The elevated expression of NQO1 in many human solid tumors along with its ability to activate quinone-based anticancer agents makes it an excellent target for enzyme-directed drug development. NQO1 plays an important role in melanogenesis and given its correlation with a poor patient outcome we propose this enzyme as an intriguing target for molecular-based therapeutic regimen against melanoma. Unfortunately, the natural product β-Lapachone (β-Lap), whose antitumor activity is based on NQO1, reported dose-limiting toxicity which hampered its pre-clinical and clinical use. Therefore, new effective and safe therapeutic NQO1-bioactivatable agents for melanoma treatment are desirable. Regarding NQO1, we demonstrated that halogenated β-Lap derivative named PFB is an excellent substrate and effective tumor-selective anticancer compound. In addition, PFB resulted more attractive than the parent β-Lap for treating metastatic-derived melanoma cells. In this context, it would be interesting to design strategies to induce NQO1 activity in cancer cells as a promising combinatorial approach with bioreductive drugs. In this sense, we had reported that photodynamic therapy (PDT) significantly upregulated NQO1 expression. Based on this event, here we demonstrated that the cytotoxic regimen consisting of PFB plus PDT improved synergistic therapeutic combination on melanoma cells. In conclusion, our contribution provides a strong rationale for using therapies that associate photo- and chemotherapy to effectively treat melanoma with modular NQO1 status.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

Combinatorial therapies;Melanoma;NQO1;Naphtoquinones;Photodynamic therapy;β-Lapachone

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