Nobiletin is capable of regulating certain anti-cancer pathways in a colon cancer cell line.

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.

Calcium fructoborate regulate colon cancer (Caco-2) cytotoxicity through modulation of apoptosis.

Sugar-borate esters have recently been reported to have anti-cancer potential. Among the sugar-borate esters, calcium fructoborate (CaFB) possesses beneficial effects on human health. Despite the beneficial effects of CaFB, there is a lack of knowledge about their mode of action in cancer. The potential cytotoxic effects of CaFB were investigated on colon cancer cells (Caco-2). The mode of action was determined through the evaluation of Fyn and Hck expression levels together with Bcl-2, Bax, and PI3K/Akt pathway proteins. CaFB treatment was found to be most effective on Caco-2 cells at 10 mM concentration for 24 h. Decreased Bcl-2 levels and increased Bax levels at 10 mM were evaluated as an indicator of apoptotic effects of CaFB. Akt, p70S6K, and 4EBP1 levels, in general, tend to decrease following CaFB, while PTEN and TSC2 levels have been found to increase. Furthermore, CaFB upregulated Hck expression and downregulated Fyn expression. In conclusion, our results indicated that CaFB treatment at 10 mM concentration, the IC50 dose found in our study, might prevent colon cancer cell proliferation both by inducing apoptosis and presumably by activating autophagy.