PT  - JOURNAL ARTICLE
AU  - Moon, Seung-Hwan
AU  - Lee, Su Jin
AU  - Jung, Kyung-Ho
AU  - Quach, Cung Hoa Thien
AU  - Park, Jin-Won
AU  - Lee, Jin Hee
AU  - Cho, Young Seok
AU  - Lee, Kyung-Han
TI  - Troglitazone Stimulates Cancer Cell Uptake of <sup>18</sup>F-FDG by Suppressing Mitochondrial Respiration and Augments Sensitivity to Glucose Restriction
AID  - 10.2967/jnumed.115.162016
DP  - 2016 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 129--135
VI  - 57
IP  - 1
4099  - http://jnm.snmjournals.org/content/57/1/129.short
4100  - http://jnm.snmjournals.org/content/57/1/129.full
SO  - J Nucl Med2016 Jan 01; 57
AB  - We evaluated how troglitazone influences cancer cell glucose metabolism and uptake of 18F-FDG, and we investigated its molecular mechanism and relation to the drug’s anticancer effect. Methods: Human T47D breast and HCT116 colon cancer cells that had been treated with troglitazone were measured for 18F-FDG uptake, lactate release, oxygen consumption rate, mitochondrial membrane potential, and intracellular reactive oxygen species. Viable cell content was measured by sulforhodamine-B assays. Results: Treatment with 20 μM troglitazone for 1 h acutely increased 18F-FDG uptake in multiple breast cancer cell lines, whereas HCT116 cells showed a delayed reaction. In T47D cells, the response occurred in a dose-dependent (threefold increase by 40 μΜ) manner independent of peroxisome proliferator-activated receptor-γ and was accompanied by a twofold increase of lactate production, consistent with enhanced glycolytic flux. Troglitazone-treated cells showed severe reductions of the oxygen consumption rate, indicating suppression of mitochondrial respiration, which was accompanied by significantly decreased mitochondrial membrane potential and increased concentration of reactive oxygen species. Troglitazone dose-dependently reduced T47D and HCT116 cell content, which was significantly potentiated by restriction of glucose availability. In T47D cells, cell reduction closely correlated with the magnitude of increase in relative 18F-FDG uptake (r = 0.821, P = 0.001). Conclusion: Troglitazone stimulates cancer cell uptake of 18F-FDG through a shift of metabolism toward glycolytic flux, likely as an adaptive response to impaired mitochondrial oxidative respiration.