Table 2 Targeted agents associated with anoikis in breast cancer

Ouabain

T47D

Activating the mitochondrial cystathionase pathway triggers anoikis

[249]

TAK-242

MDA-MB-231, MCF-7, SKBR3, BT-474

Increasing anoikis by altering NF-кB and p53 related apoptosis genes in BC cells

[250]

SAHA and TRAIL

MDA-MB-231, MCF-7

Activating caspase-3, phosphorylation of EGFR, reduction of phosphorylated ERK1/2, induction of reduction of Phosphorylated BimEL, and increase of BimEL dephosphorylated form, promoting anoikis

[251]

Berberine

MDA-MB-231, MCF-7

Inducing cell cycle arrest to promote anoikis resistance

[252]

4-methylumbelliferone (4-MU)

MDA-MB-231, MCF-7

Regulating hyaluronic acid/HAS2/CD44 and specific matrix effectors, increasing anoikis

[253]

Curcumol

MDA-MB-231, IV2

Regulating the YAP1/Skp2 molecular pathway, promoting anoikis

[254]

isoliquiritigenin

MDA-MB-231, BT-549

Down–regulating COX-2 and CYP4A signaling; decreasing the expression levels of phospho-PI3K (Tyr(458)), phospho-PDK (Ser(241)) and phospho-Akt (Thr(308)), promoting anoikis

[255]

archazolid

MDA-MB-231, 4T1, T24, 5637

Reducing expression of c-FLIP, activation of caspase-8, and early increase in active integrin-β1 and pro-anoikis protein BIM

[256]

pygenic acid A (PA)

MDA-MB-231, 4T1

Down-regulating pro-survival proteins such as cIAP1, cIAP2 and survival; down-regulating anoikis resistance proteins such as p21, cyclin D1, p-STAT3 and HO-1

[257]

Disulfiram (DSF)

MDA-MB-231, 4T1

Inhibiting focal adhesion, regulating waveform proteolysis, and activating calpain, promoting anoikis

[258]

pretubulysin

MDA-MB-231, 4T1

Activation of mitogen-activated protein kinases (especially JNK (c-Jun N-terminal kinase)) and phosphorylation of Mcl-1, induces proteasomal degradation of Mcl-1, promoting anoikis

[259]

Epoxyazadiradione

MDA-MB-231

Reducing EGFR expression, promoting anoikis, inhibits colony formation, downregulating MMP-9 and fibronectin, induces G2/M phase block, downregulating cyclin A2/cdk2, interfering with cellular metabolism and inhibiting nuclear translocation of nuclear factor NF-kB

[260]

Tubeimoside V

MDA-MB-231

Inhibition of non-anchored culture-induced CAV-1 overexpression, EGFR activation, and ITGB1-FAK activation, promoting anoikis

[261]

Goniothalamin(GTN)

MDA-MB-231

GTN reverses EMT, inhibits EGFR, FAK and Src pathways, reduces matrix metalloproteinase secretion, increases E-cadherin protein and decreases N-cadherin levels, promoting anoikis

[262]

HPW-RX40

MDA-MB-231

Inhibiting integrin expression and activation and shedding-induced FAK activation and downstream phosphorylation of Src and pilein, promoting anoikis

[263]

Ziyuglycoside II

MDA-MB-231

Regulating Src/EGFR-dependent ITGB4/FAK signaling pathway, promoting anoikis

[264]

Salinomycin

MDA-MB-231

Inhibiting STAT3 activation and reduces CD44 + /CD24- stem cell-like populations, promoting anoikis

[265]

Dieldrin

MDA-MB-231

Increasing resistance to anoikis and TrkB expression

[266]

Metformin and 2-deoxy glucose

MDA-MB-231

Strong activation of AMPK increases phosphorylation of ACC, which increases the G2/M phase cell population and triggers G2 and mitotic (M) phase arrest of the cell cycle, promoting anoikis

[267]

5-azacytidine (5-AzaC)

MCF-7

Nucleoside analogs that reduce DNA methylation, induce anoikis, inhibit mammosphere formation and reduce metalloproteinase 9 activity, promoting anoikis

[268]

Pt(O,O'-acac)(gamma-acac)(DMS)

MCF-7

Activating PKC-α, which generates ROS, leads to increased Ca(2 +) permeability and decreased PMCA activity, promoting anoikis

[269]

BKM120 Joint ATO

MCF-7

BKM120 enhances ATO-induced anti-proliferative effects by inducing G1 phase block and reducing DNA synthesis in BrdU-treated cells, promoting anoikis

[270]

Benzothiazole carbamates and amides

MCF-7

Inducing anoikis, G2/M cell cycle arrest and reducing ROS levels

[271]

PS, JCP1 and JCP2 extracts

MCF-7

Inhibition of β1-integrin expression, F-actin, cell detachment, promoting anoikis

[272]

Pt(O,O'-acac)(gamma-acac)(DMS)

MCF-7

Inducing anoikis and alters cell migration, anchorage independence, matrix interactions, and MMP activity

[273]

2-Deoxy-D-Glucose

Hs578T, Hs578Ts(i) 8

Decreasing oxidative phosphorylation, increase glycolysis, and inhibit tumor migration and invasion, promoting anoikis

[274]

Aspirin

4T1, E0771

Aspirin targets thromboxane A2 (TXA2), TXA2 receptor (TP) and thromboxane A2 synthase 1 (TBXAS1) are upregulated in metastatic BC cells and confer anoikis resistance through sustained activation of Akt

[275]

Monascin (MS)

4T1

Inhibiting E-cadherin and β-catenin expression in cells, promoting anoikis

[276]