Sammanfattning

Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells.

Nyckelord

Iron(II) chelate, cancer, therapy, proliferating cells, quiescent cells

Publicerad i

Scientific Reports
2016, Volym: 6, artikelnummer: 38343

SLU författare

• Persson, Ingmar

  • Institutionen för kemi och bioteknologi, Sveriges lantbruksuniversitet
    

Globala målen

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UKÄ forskningsämne

Läkemedelskemi
Biomaterialvetenskap


Publikationens identifierare

DOI: https://doi.org/10.1038/srep38343

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/78343