Table 3 AKT inhibition activates FOXO3a in breast cancer cells

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