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A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo.

Abstract：

:Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here we demonstrate that the natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP. Polydatin blocks G6PD causing accumulation of reactive oxygen species and strong increase of endoplasmic reticulum stress. These effects are followed by cell cycle block in S phase, an about 50% of apoptosis, and 60% inhibition of invasion in vitro. Accordingly, in an orthotopic metastatic model of tongue cancer, 100 mg/kg polydatin induced an about 30% tumor size reduction with an about 80% inhibition of lymph node metastases and 50% reduction of lymph node size (p < 0.005). Polydatin is not toxic in animals up to a dose of 200 mg/kg and a phase II clinical trial shows that it is also well tolerated in humans (40 mg twice a day for 90 days). Thus, polydatin may be used as a reliable tool to limit human cancer growth and metastatic spread.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Mele L,Paino F,Papaccio F,Regad T,Boocock D,Stiuso P,Lombardi A,Liccardo D,Aquino G,Barbieri A,Arra C,Coveney C,La Noce M,Papaccio G,Caraglia M,Tirino V,Desiderio V

doi

10.1038/s41419-018-0635-5

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

572

issue

5

issn

2041-4889

pii

10.1038/s41419-018-0635-5

journal_volume

9

pub_type

杂志文章

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