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

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

  • Cell Death Dis. 2018 May 1;9(5):572. doi: 10.1038/s41419-018-0635-5.
Luigi Mele 1,  Francesca Paino 1,  Federica Papaccio 2,  Tarik Regad 3,  David Boocock 3,  Paola Stiuso 4,  Angela Lombardi 4,  Davide Liccardo 1,  Gabriella Aquino 5,  Antonio Barbieri 6,  Claudio Arra 6,  Clare Coveney 3,  Marcella La Noce 1,  Gianpaolo Papaccio 7,  Michele Caraglia 8,  Virginia Tirino 1,  Vincenzo Desiderio 1
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  • 2 Oncologia Medica ed Ematologia, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale "F. Magrassi e A. Lanzara", University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  • 3 The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, NG1 4FQ, Nottingham, UK.
  • 4 Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  • 5 Department of Research, Pathology Unit, Istituto Nazionale Tumori- IRCCS- Fondazione Pascale, 80131, Naples, Italy.
  • 6 SSD Sperimentazione Animale, Istituto Nazionale Tumori- IRCCS- Fondazione Pascale, 80131, Naples, Italy.
  • 7 Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. gianpaolo.papaccio@unicampania.it.
  • 8 Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. michele.caraglia@unicampania.it.
PMID: 29760380 DOI: 10.1038/s41419-018-0635-5
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z