FLUX FORMULA SKIN

Unlike other chelating agents, DFP readily enters cells and reaches the major intracellular sites of iron accumulation ( 8).

FLUX FORMULA SKIN

Although mostly used clinically for the treatment of thalassemia ( 4), Friedreich ataxia ( 5), and kidney disease ( 6), DFP has also been shown to inhibit proliferation of skin fibroblasts and frataxin-depleted neuroblastoma-derived cells in vitro ( 7, 8). Thus, no cancer treatment options targeting intracellular iron are clinically available yet.Дeferiprone (DFP) is an orally administered iron-chelator, used clinically ( 3). Although iron has been suggested as a potential chemotherapeutic target ( 2), most available iron-chelating agents target extracellular iron, leading to systemic iron deficiency and toxicity. while potentially toxic to cells and tissues, it is also essential for cancer cell growth and proliferation ( 1). Iron is known to have both beneficial and deleterious effects in tumor cells, i.e. Our results indicate the potential of DFP to inhibit prostate cancer proliferation at clinically relevant doses and plasma concentrations. At this time point, all cell lines studied showed (iii) significant decreases in mitochondrial functional parameters associated with oxygen consumption rate, and (iv) both significantly lower m-Acon expression and activity. Exposure to 100 ОјM DFP led to: (i) Significant inhibition of cell migration after different exposure times, ranging from 12 h (TRAMP-C2) to 48 h (22rv1), in agreement with the respective cell doubling times (ii) Significantly decreased glucose consumption and glucose-driven TCA cycle activity in metastatic TRAMP-C2 cells, during the first 10 h of exposure, and impaired cellular bioenergetics and membrane phospholipid turnover after 23 h exposure, consistent with a cytostatic effect of DFP. The half and 90% inhibitory concentration (IC 50 and IC 90, respectively) of DFP for the three cell lines after 48 h incubation ranged within 51вЂ“67 ОјM and 81вЂ“186 ОјM, respectively.

The effects of DFP were evaluated at different cellular levels: cell culture proliferation and migration metabolism of live cells (time-course multi-nuclear magnetic resonance spectroscopy cell perfusion studies, with 1- 13C-glucose and Seahorse extracellular flux analysis) and expression (Western Blot) and activity of mitochondrial aconitase (m-Acon), an iron-dependent enzyme. We studied the effects of Deferiprone (DFP), a chelator of intracellular iron, on three prostate cancer cell lines: murine, metastatic TRAMP-C2 murine, non-metastatic Myc-CaP and human, non-metastatic 22rv1. Cancer growth and proliferation rely on intracellular iron availability.

Flux formula