Table 1 Specific mechanisms and target effectors involved in the ConA-mediated- apoptotic or autophagic cell death, hepatitis, fibroblast activation, and angiogenesis (in vitro studies)
Cancer cell type | ConA concentration (µg/ml) | Target(s) | The specific mechanism(s) | References |
|---|---|---|---|---|
KK-47 bladder | 0.2–20 | DNA fragmentation, cytoskeleton reorganization | Inhibiting RNA synthesis | [15] |
U87 glioblastoma | 30 | LRP-1 | LRP-1 down-regulation and mistrafficking, disrupt cytoskeleton integrity | [17] |
Human melanoma A375 | 25 | Caspase 9 and 3, cyto.c, ICAD, PARP | Caspase-dependent apoptosis | |
Glioma cell lines (UWR2, UWR3, U2S1MG, and SNB-19) | 100 | Gelatinase A, MT1-MMP | Inducing malignant progression by MT-MMP/MMP2 up-regulation | [21] |
3Y1 | 5–20 | c-Ras, MT1-MMP, MMP-2/9 | c-Ras-dependent activation of the MMPs | [23] |
U87 human glioma cells, COS-7 | 10 | MT1-MMP, pro-MMP2 | pro-MMP2 activation through the proteolytic activity of MT1-MMP | [24] |
MDA-MB-231 | 20 | proMT1-MMP | Inhibiting MT1-MMP maturation by decreasing calcium levels | [25] |
MDA-MB-231 | 20 | MT1-MMP, proMMP2 | Increase MMP2 levels by inducing tyrosine phosphorylation | [27] |
HEK293T and HSC-4 | 30 | MT1-MMP, HAI-1, Matripase | Increase matriptase protease activity through the cleavage of HAI-1 | [28] |
Mesenchymal stromal cells(MSC) | 30 | MT1-MMP, STAT3 | Increase COX2 expression via MT1-MMP/JAK/STAT3 signaling | [29] |
Bone marrow-derived dendritic cells (BMDC) | 10 | ALT, AST, IL-12, IFN-γ, P62 | Increase the maturation of BMDCs by aberrant regulation of autophagy, thereby augmenting cytokine secretion | [33] |
Mesenchymal stromal cells(MSC) | 30 | MT1-MMP, STAT3, Src | Up-regulate CSF1-2-3 secretion through TLR-2/6 activation | [36] |
HeLa, Caco-2, and A549 | 2–50 | BAD, Bcl-2, CASP-3/9, AKT | Inhibiting the receptor of tyrosine kinases by aggregating them in lipid rafts and inducing apoptosis | [39] |
U87 glioblastoma | 10 | MT1-MMP, MMP2, G6PT, Akt | Inhibiting G6PT and Akt by MT1-MMP cytoplasmic domain, inducing apoptosis | [41] |
HeLa | 54 | Beclin-1, LC3-I/II, Akt, MEK | Inducing autophagy by activating PI3K/Akt/mTOR and MEK/ERK pathways | [42] |
SKOV3, MDAH041, SKP53, and TR9-7 | 15–20 | FOXO1a, Bim, p53, p21, p27 | Inducing apoptosis by activating FOXO1a-Bim signaling | [43] |
MCF-7 and MCF-10A | 1–100 | Caspase 9 and 3, Cyto.c, Bax, Bid, Bcl-2, Bcl-XL, NF-κB, ERK, JNK, p53, p21, CDK-1/2 | Inducing caspase-dependent apoptosis | [44] |
MDAH041, TR9-7, and SKOV3 | 15 | Bax, Bcl2, p73, p21, Foxo1a, Bim, Akt | Inducing p73-mediated apoptosis | [45] |
Human leukemia MOLT-4 and HL-60 | 1–200 | DNA fragmentation, cytoskeleton reorganization | Inducing apoptosis | [47] |
ML-1, CT-26, Huh-7, and HepG2 | 7.7–20 | Beclin-1, ATG5, LC3-I/II, BNIP3, Akt, COX-4 | Inducing BNIP3-mediated autophagy | [48] |
U87 glioblastoma | 30 | MT1-MMP, MMP2, NANOS1, BNIP3, STAT3, ATG-3/12/16L1/16L2, COX2, Akt | Inducing autophagy through the intracellular domain of MT1-MMP | |
Human umbilical vein endothelial and Ea.hy926 endothelial cells | 0.3–3 | Akt, ERK, p21, p27, p38, Cyclin D1, Cyclin E | Promoting angiogenesis through Akt/ERK/Cyclin D1 axis | [55] |
BALBlc 3T3 fibroblasts, human gingival fibroblasts (HGF) | 50 | DNA fragmentation, cytoskeleton reorganization | Cell cycle arrest, inhibiting DNA and RNA synthesis | [56] |
Human fibroblast and COS7 | 20–50 | TIMP-2, SHP-2, ERK, p38, MMP2, Ras, SOS-1, Grb-2 | SHP-2-mediated upregulation of TIMP-2, thereby fibroblast proliferation | |
CD4+ T cells | 10 | IFN-γ, TNF-α, IL-4/6/10/12, STAT-1/3, p65 | CD24 aggravates ConA-induced liver injury | [72] |
Liver mononuclear cells | 10 | IFN-γ, TNF-α, IL-4, FasL | Va14 NKT Cells develop ConA-induced hepatitis through IL-4 production | [73] |
ML-1, HuH-7, and Hep G2 | 20 | LC3-I/II, Casp3, STAT3, MIF, BNIP3 | Inducing STAT3-MIF-BNIP3-mediated autophagy in the hepatoma cells |