Discovery of Isoplumbagin as a Novel NQO1 Substrate and Anti-Cancer Quinone.

Autor: Tsao YC; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan., Chang YJ; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan., Wang CH; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan., Chen L; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.; Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Jun 19; Vol. 21 (12). Date of Electronic Publication: 2020 Jun 19.
DOI: 10.3390/ijms21124378
Abstrakt: Isoplumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone), a naturally occurring quinone from Lawsonia inermis and Plumbago europaea , has been reported to have anti-inflammatory and antimicrobial activity. Inflammation has long been implicated in cancer progression. In this study, we examined the anticancer 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 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (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 reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] dehydrogenase quinone 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 anticancer activity of isoplumbagin mainly through modulating mitochondrial dynamics and function.
Databáze: MEDLINE