β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer

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Abstract

Cancer, one of the major health problems all over the world, requires more competent drugs for clinical use. One recent possible chemotherapeutic drug under research is β-lapachone. β- lapachone (1,2-naphthoquinone) has promising activity against those tumors showing raised levels of Nicotinamide di-phosphate Quinone Oxidoreductases-1 (NQO1). NQO1 is found to be up-regulated in pancreatic tumor cells, and thus β-lapachone could generate cytotoxicity in various cancers like pancreatic tumors. β-lapachone harborage independent growth and clonogenic cell survival in agar. The cell-killing effects of β-lapachone can be stopped by using dicumarol, an inhibitor of NAD(P)H Quinone Oxidoreductases-1. In previously established pancreatic cancer xenografts in mice, β- lapachone inhibited the tumor growth when given orally rather than when combined with cyclodextrin to improve its bioavailability.

Keywords: NAD(P)H quinone oxidoreductase-1, β-lapachone, reactive oxygen species, quinones, cyclodextrins, human pancreatic cancer.

Graphical Abstract

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