Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-stimulated Radioiodide Accumulation in Thyroid Cells
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Date
2014-02
Authors
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Publisher
Mary Ann Liebert, Inc.
Abstract
Background: Selectively increased radioiodine accumulation in thyroid cells by thyrotropin (TSH) allows targeted treatment of thyroid cancer. However, the extent of TSH-stimulated radioiodine accumulation in some thyroid tumors is not sufficient to confer therapeutic efficacy.
Hence, it is of clinical importance to identify novel strategies to selectively further enhance TSH-stimulated thyroidal radioiodine accumulation.
Methods: PC Cl3 rat thyroid cells, PC Cl3 cells overexpressing BRAFV600E, or primary cultured tumor cells from thyroid cancer mouse model, under TSH stimulation were treated with various reagents for 24 hrs. Cells were then subjected to radioactive iodide uptake, kinetics, efflux assays, and protein extraction followed by western blotting against selected antibodies.
Results: We previously reported that Akt inhibition increased radioiodine accumulation in thyroid cells under chronic TSH stimulation. Here, we identified Apigenin, a plant-derived flavonoid, as a reagent to further enhance iodide influx rate increased by Akt inhibition in thyroid cells under acute TSH stimulation. Akt inhibition is permissive for Apigenin’s action, as Apigenin alone had little effect. This action of Apigenin requires p38 MAPK activity, but not PKC-δ. The increase in radioiodide accumulation by Apigenin with Akt inhibition was also observed in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβPV/PV mice.
Conclusion: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer.
Description
Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
This is a copy of an article published in Thyroid © 2014 [copyright Mary Ann Liebert, Inc.]; Thyroid is available online at: http://online.liebertpub.com.
This is a copy of an article published in Thyroid © 2014 [copyright Mary Ann Liebert, Inc.]; Thyroid is available online at: http://online.liebertpub.com.
Keywords
thyroid cancer, radioiodine accumulation, Akt inhibition, Apigenin
Citation
Aparna Lakshmanan, Andrea I. Doseff, Matthew D. Ringel, Motoyasu Saji, Bernard Rousset, Xiaoli Zhang, and Sissy M. Jhiang, "Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-stimulated Radioiodide Accumulation in Thyroid Cells," Thyroid. 2014, ahead of print. doi:10.1089/thy.2013.0614.