Abstract
Natural 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 µM, 264 µM, and 40 µM, 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 µM, respectively. Nobiletin decreased HO-1 and VEGF levels at concentrations greater than 100 µM. MMP-7 levels interestingly increased at 100 µM but decreased at doses greater than 250 µM. 4EBP1 levels increased, except from 2000 and 3000 µM nobiletin concentrations. Tuberin levels increased at 10, 50, and 3000 µM, decreased at 250 µM, 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 µM 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 µM. These results are significant as a nobiletin therapy could prevent colon cancer progression by inhibiting Akt signaling and angiogenesis.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The study design, biochemical analysis and interpretation of results, and writing the article were done by MAK. The sole author declares that all data were generated in-house and that no paper mill was used.
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Kisacam, M.A. Nobiletin is capable of regulating certain anti-cancer pathways in a colon cancer cell line. Naunyn-Schmiedeberg's Arch Pharmacol 396, 547–555 (2023). https://doi.org/10.1007/s00210-022-02354-9
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DOI: https://doi.org/10.1007/s00210-022-02354-9