Generation of a Difluoromethylornithine (DFMO) Resistant Cell Line in a Polyamine Depletion Strategy

Abstract

Polyamines are essential growth factors for normal and malignant cells. Cells obtain polyamines via biosynthesis or transport from the extracellular environment and polyamine depletion therapy is an attractive option to inhibit the growth of cancer cells. Previous reports have indicated that depletion therapy (e.g. androgen depletion in prostate cancer) can lead to epigenetic changes resulting in resistance to the therapy and aggressive metastatic cancer. We were interested to know if polyamine depletion driven by treatment with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO) could lead to similar outcomes. The pancreatic cancer cell line Panc‐1 was passaged for 10 generations on IC50 and IC75 concentrations of DFMO, after which a decreased sensitivity to DFMO was observed. Our results indicate the need for further investigation into the mechanism of resistance to DFMO, and it's potential consequences for clinical outcomes.Support or Funding InformationUniversity of Central Florida, College of Sciences Seed AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.