Diverse roles of FOXO family members in gastric cancer

Table 1 Molecules targeting FOXOs and related proteins for potential gastric cancer therapy

Molecule	Targets	Mechanism	Effects	Ref.
Luteolin	FOXO1	Increases FOXO1 expression	Represses GC cell growth	Ding et al[127]
Celecoxib	Akt, GSK3b, FOXO1, and caspase-9	Downregulates Akt, GSK3b, and FOXO1 and upregulates caspase-9 in the mitochondrial apoptotic pathway	Represses GC cell growth	Kim et al[128]
4-Amino-2-trifluoromethyl-phenyl retinate	14-3-3ε	Downregulates expression of 14-3-3ε, resulting in increased expression of FOXO1 and P27kip1, decreased expression of CDK2 and cyclin E, and decreased activity of AKP and LDH. Blocks the cell cycle at G0/G1 phase	Inhibits cell proliferation and induces cell differentiation	Xia et al[129]
Gramicidin	FOXO1	Decreases phosphorylation of FOXO1 and down-regulates the expression of cyclinD1 and Bcl-2, leading to G2/M cell cycle arrest	Inhibits cell proliferation	Chen et al[130]
Olaparib	PARP1	Inhibits PARP1 and thus induces G2/M cell cycle arrest by activating FOXO3	Inhibits cell proliferation	Park et al[126]
Bacillomycind-C16	Akt and FOXO3	Inhibits phosphorylation of Akt and increases the level of FOXO3 protein	Induces apoptosis	Lin et al[131]
Protein arginine methyltransferase 1	FOXO1 and BAD	Activates FOXO1 and BAD	Induces chemosensitivity	Altan et al[132]
Sphingosine kinase 1	FOXO1 and FOXO3	Attenuates the transcriptional activity of FOXO1 and FOXO3 via promoting PI3K/Akt-mediated phosphorylation	Enhances proliferation (targeting FOXO1) and resistance to apoptosis (targeting FOXO3)	Xia et al[91] and Xiong et al[133]
Hsa_circ_0001368	miR-6506-5p	Acts as a competing endogenous RNA for miR-6506-5p and inhibits the downregulation by miR-6506-5p on FOXO3	Inhibits tumor growth	Lu et al[134]
miR-1274a	FOXO4	Inhibits FOXO4 expression	Promotes tumor growth and migration	Wang et al[94]