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

被引:19
作者
Tsao, Yen-Chi [1 ]
Chang, Yu-Jung [1 ]
Wang, Chun-Hsien [1 ]
Chen, Linyi [1 ,2 ]
机构
[1] Natl Tsing Hua Univ, Inst Mol Med, Hsinchu 30013, Taiwan
[2] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 30013, Taiwan
关键词
isoplumbagin; NQO1; quinone; cancer; metastasis; CANCER; ACTIVATION; CELLS;
D O I
10.3390/ijms21124378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Isoplumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone), a naturally occurring quinone fromLawsonia inermisandPlumbago 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.
引用
收藏
页码:1 / 17
页数:16
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