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Table 3 AKT inhibition activates FOXO3a in breast cancer cells

From: Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review

First author (Year) Treatment Effect on FOXO3a (Activates/Inactivates) Cellular effects
Brandi (2013) [27] Indole-3-carbinol cyclic tri- and tetrameric derivatives, specific target unknown but inhibits AKT directly or indirectly. Activates in MCF-7 and MDA-MB-231 breast cancer cell lines) and in vivo in a tumour xenograft measured as nuclear translocation of FOXO3a. Increased expression of p21 cip1, p27 kip1 and decreased ER expression.
Li (2007) [29] Selenium and Doxorubicin via p38 mediated inhibition of AKT. Activates in MCF7 measured by P-FOXO3a and reporter assay. Increased Bim expression and apoptosis.
Sharma (2012) [33] 18β-glycyrrhetinic acid (GRA) specific target unknown but inhibits AKT directly or indirectly. Activates in MCF7 but not normal breast cell line MCF-10 measured as increased expression and nuclear translocation. Increased Bim expression and caspase-dependent apoptosis.
Sunters (2006) [32] Paclitaxel inhibits AKT via JNK Activates in MCF7 measured as nuclear localisation of FOXO3a. JNK1 activation and apoptosis in MCF7 and also in a panel of other cells lines MT 3522, 734 B, ZR-75-1, T47-D, CAL-51, CAMA-1, MDA-MB-231, and SKBR-7.
Xie (2010) [31] SZ-685C (marine anthraquinone) specific target unknown. Inhibits AKT directly or indirectly. Activates in MCF-7 and MDA-MB-435. AKT inhibition.
Increased Bim.
Increased apoptosis.
Increased caspase activity.
Zhao (2013) [30] 5,7-dihydroxy-8-nitrochrysin (NOC)-specific target unknown. Inhibits AKT directly or indirectly. Activates in MDA-MB-453. Increased Bim expression
Increased apoptosis.
Lin (2011) [28] FLOT1 silencing associated with suppression of Akt activity Activates in MCF7 and MDA-231 measured as expression level and P-FOXO3a. Up-regulation of p21 cip1 and p27 kip1