Table 3.

AKT inhibition activates FOXO3a in breast cancer cells

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