β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers.

Abstract

NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.

• Authors: Yang Yang, Xianchun Zhou, Ming Xu, Junjie Piao, Yuan Zhang, Zhenhua Lin, Liyan Chen
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 2681 (06 02 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28578385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Naphthoquinones
• beta-lapachone
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human

Topics

• Animals
• Biomarkers, Tumor
• Breast Neoplasms (genetics, metabolism, mortality, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Disease Progression
• Dose-Response Relationship, Drug
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Female
• Gene Expression
• Humans
• Mice
• NAD(P)H Dehydrogenase (Quinone) (genetics, metabolism)
• Naphthoquinones (pharmacology)
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Xenograft Model Antitumor Assays