Curcumin Inhibits the PPARδ-p-Akt-GLUT1 Pathway and Ameliorates the Antiproliferative Effects of Doxorubicin in MDA-MB-231 Cells.

OBJECTIVE: The aim of the present study was to examine whether GLUT1 was involved in the antiproliferative activity of curcumin and doxorubicin by understanding mechanistically how curcumin regulated GLUT1. METHODS: Expression level of GLUT1 in MCF-7 and MDA-MB-231 cells were quantitated using quantitative real-time PCR and western blot. GLUT1 activity was inhibited in MDA-MB-231 cells with the pharmacological inhibitor WZB117 to assess the anti-proliferative effects of doxorubicin using MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide).  To examine cell proliferation, trypan blue assay was used in cells transfected with GLUT1 siRNA or plasmid overexpressing GLUT1 with doxorubicin and/or commercially available curcumin. The role of PPARδ and Akt on the regulation of GLUT1 by curcumin was examined by overexpressing these proteins and western blot was employed to examine their protein expression. RESULTS: The data revealed that there was a 1.5 fold increase in GLUT1 mRNA and protein levels in MDA-MB-231 compared to MCF-7.  By inhibiting GLUT1 in triple negative breast cancer cell line, MDA-MB-231 with either the pharmacological inhibitor WZB117 or with GLUT1 siRNA, we observed the enhanced antiproliferative effects of doxorubicin. Additional observations indicated these effects can be reversed by the overexpression of GLUT1. Treatment of MDA-MB-231 with curcumin also revealed downregulation of GLUT1, with further growth suppressive effects when combined with doxorubicin.  Overexpression of GLUT1 blocked the growth suppressive role of curcumin and doxorubicin (p< 0.05). Mechanistically, we also observed that the regulation of GLUT1 by curcumin was mediated by the Peroxisome proliferator-activated receptor (PPAR) δ/Akt pathway. CONCLUSION: Our study demonstrates that regulation of GLUT1 by curcumin via the PPARδ/Akt signaling improves the efficacy of doxorubicin by promoting its growth inhibitory effects in MDA-MB-231 cells.

Equal pay for equal work in radiology: Expired excuses and solutions for change.

The gender pay gap is not a problem of the past. Women continue to receive less pay for equal work and radiology is one of four medical specialties with the largest gender pay gap. Numerous social factors contribute to the gender pay gap; however, radiology can close the gender pay gap through intentional strategies, including acknowledging the gender pay gap, eliminating bias and minority taxes through progressive compensation and parental leave models, devaluing overwork, developing longitudinal mentorship and sponsorship, and demanding transparent institutional policies. Patient care and overall organizational success will improve when the barriers resulting in the gender pay gap are eliminated.

Non-small-cell lung cancer associated with excessive eosinophilia and secretion of interleukin-5 as a paraneoplastic syndrome.

Eosinophilia associated with solid tumors is an infrequent occurrence. The pathogenesis of tumor-associated eosinophilia is not well understood. Interleukin-5 (IL-5) is a cytokine that has been implicated in the development of eosinophilia in mice and humans. However, there is little data associating IL-5 production with eosinophilia in the presence of tumor. We report, in a patient with locally advanced NSCLC, the presence of excessive eosinophilia and elevated serum IL-5 levels at diagnosis. Immunohistochemical staining of the primary tumor showed large amounts of intracellular IL-5. Both eosinophil count and IL-5 levels normalized after surgical removal of the tumor. Tumor-associated eosinophilia observed in this case is mediated by IL-5. The production of IL-5 is related to the presence of the tumor.