Kisacam, Mehmet A. A.2024-09-182024-09-1820230028-12981432-1912https://doi.org/10.1007/s00210-022-02354-9https://hdl.handle.net/20.500.12483/10108Natural remedies have the potential to improve conventional cancer therapies and enhance patient outcomes. Citrus polymethoxyflavone nobiletin has been demonstrated to have anticancer effects on several cancer cell lines. In this study, the anti-cancer activity of nobiletin is investigated on Bax, Bcl-2, HO-1, VEGF, MMP-7, Akt, p70S6K, 4EBP1, tuberin, and hamartin. IC50 doses were 403.6 mu M, 264 mu M, and 40 mu M, respectively, at 24, 48, and 72 h. Akt, Bax, Bcl-2, and p70S6K levels decreased at nobiletin concentrations greater than 100, 250, 500, and 1000 mu M, respectively. Nobiletin decreased HO-1 and VEGF levels at concentrations greater than 100 mu M. MMP-7 levels interestingly increased at 100 mu M but decreased at doses greater than 250 mu M. 4EBP1 levels increased, except from 2000 and 3000 mu M nobiletin concentrations. Tuberin levels increased at 10, 50, and 3000 mu M, decreased at 250 mu M, and remained unchanged at the rest of the concentrations. Nobiletin decreased hamartin levels; however, this decrease was statistically significant only at 10, 100, 250, 500, and 3000 mu M concentrations. Decreased Akt activity might be interpreted as nobiletin inhibiting mTORC1 activity and subsequently increased 4EBP1 and unchanged or decreased p70S6K protein levels. Akt activity can cause suppression of angiogenesis via decreased VEGF, MMP-7, and HO-1 levels at concentrations greater than 500 mu M. These results are significant as a nobiletin therapy could prevent colon cancer progression by inhibiting Akt signaling and angiogenesis.eninfo:eu-repo/semantics/closedAccessFlavonoidsNobiletinColon cancerAktAngiogenesisArticle396354755510.1007/s00210-022-02354-9364542562-s2.0-85143231485Q2WOS:000914905000001Q2