RRx-001, a novel clinical-stage chemosensitizer, radiosensitizer, and immunosensitizer, inhibits glucose 6-phosphate dehydrogenase in human tumor cells

Bryan Oronsky, Jan Scicinski, Tony Reid, Arnold Oronsky, Corey Carter, Neil Oronsky, Pedro Cabrales

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The anti-proliferative effects of RRx-001, a novel RONS-mediated immuno-epigenetic and vascular normalizing anticancer agent in Phase 2 clinical trials, are not explainable via a single mechanism. Previous research suggested an association between G6PD inhibition and RRx-001 anticancer activity. The results in this study confirm and extend previous observations that RRx-001 exerts its anti-proliferative effect, at least partially, through interference with glucose 6 phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway, responsible for maintaining adequate levels of the major cellular reductant, NADPH. RRx-001 affects glucose and G6PD enzyme activity in three different cancer cell lines namely Hep G2, CACO-2, and HT-29. We observed that in all cancer cell lines tested, RRx-001 induced G6PD inhibition in a concentration dependent fashion. Inhibition of G6PD activity associated with a reduction in ribonucleotide synthesis, glutathione reduction and cell proliferation may represent an important mechanism by which RRx-001 exerts its anticancer effects.

Original languageEnglish (US)
Pages (from-to)251-265
Number of pages15
JournalDiscovery Medicine
Volume21
Issue number116
StatePublished - 2016

ASJC Scopus subject areas

  • General Medicine

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