Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone

Tsao, Y.-C.; Chang, Y.-J.; Wang, C.-H.; Chen, L.

doi:10.1101/2020.04.28.063222

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bioRxiv · 10.1101/2020.04.28.063222

Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone

Tsao, Y.-C.·Chang, Y.-J.·Wang, C.-H.·Chen, L.

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Abstract

Isoplumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone), a naturally occurring quinone from Lawsonia inermis and Plumbago europaea, that has been reported to have anti-inflammatory and anti-microbial activity. Inflammation has long been implicated in cancer progression. In this study, we examined the anti-cancer effect of chemically-synthesized isoplumbagin. Our results revealed that isoplumbagin treatment suppressed cell viability and invasion of highly invasive oral squamous cell carcinoma (OSCC) OC3-IV2 cells, glioblastoma U87 cells, non-small cell lung carcinoma H1299 cells, prostate cancer PC3 cells, and cervical cancer Hela cells by using MTT and Boyden chamber assays. In vivo studies demonstrate the inhibitory effect of 2 mg/kg isoplumbagin on the growth of orthotopic xenograft tumors derived from OSCC cells. Mechanistically, isoplumbagin exerts its cytotoxic effect through acting as a substrate of NAD(P)H quinone dehydrogenase 1 (NQO1) to generate hydroquinone, which reverses mitochondrial fission phenotype, reduces mitochondrial complex IV activity and thus compromises mitochondrial function. Collectively, this work reveals an anti-cancer activity of isoplumbagin mainly through modulating mitochondrial dynamics and function. Chemical compounds: Isoplumbagin (PubChem CID: 375105)

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Tsao, Y.-C., Chang, Y.-J., Wang, C.-H., Chen, L.. 2020-04-30. Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone. https://doi.org/10.1101/2020.04.28.063222

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