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FoxO1: a potential target of cinnamon extract on the PI3K cascade
Author(s) -
Borgman Rachael,
Pearce Kathryn,
Aulthouse Amy,
Stockert Amy
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09692
Subject(s) - foxo1 , glut4 , rosiglitazone , pi3k/akt/mtor pathway , transcription factor , regulator , cell culture , microbiology and biotechnology , glucose transporter , medicine , biology , endocrinology , cancer research , chemistry , diabetes mellitus , biochemistry , signal transduction , gene , insulin , genetics
Cinnamon has long been used medicinally for digestive discomforts. Literature highlights anti‐diabetic properties of cinnamon in cell culture and human clinical studies, suggesting a potential role for type 2 diabetes therapy. Despite these studies and patients’ use of cinnamon, the therapeutic mechanism is still poorly understood. Transcription factor PPAR‐gamma has been identified as one potential target of the cinnamon extract components given the effects of cinnamon on morphological changes in the 3T3‐L1 cells during treatment. We confirmed the presence of PPAR‐gamma in 3T3‐L1 cells using immunohistochemistry providing evidence for the spontaneous differentiation of cells when grown in three‐dimensional culture. Furthermore, we have characterized morphological changes in cinnamon‐treated cells while grown in monolayer and sought to determine what expression changes occur under these growth conditions. Due to the changes in expression that we observed, we identified FoxO1 as a potential target of the cinnamon extract. FoxO1 is a metabolic regulator that has been implemented in lipid localization, aging, and cell death. In addition to PPAR‐gamma, expression and localization of GLUT4 transporters is up‐regulated with cinnamon treatment in both muscle and adipose. Interestingly, FoxO1 is involved with both PPAR‐gamma and GLUT4 expression and activities, making it a reasonable target of the extract. Together, these data suggest that cinnamon not only affects multiple targets, but is also likely involved at several stages in the PI3K cascade. In addition to examining the expression levels of FoxO1 in treated and untreated cells, we sought to explore the localization of the FoxO1 transcription factor as it is proposed to shuttle between the nucleus and cytoplasm depending on conditions. We have initiated immunocytochemistry studies to determine the relative localization of the transcription factor when treated with cinnamon extract as compared to no treatment in order to correlate the location to the expression data. Support or Funding Information Ohio Northern University Raabe College of Pharmacy Bower, Bennett and Bennett Research Award