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Table 2 In vitro anti-cancer effects of CDDO-Me on various solid cancer cells

From: Preclinical evidences toward the use of triterpenoid CDDO-Me for solid cancer prevention and treatment

Cellular effects

Mechanisms

Concentration

Reference

Inhibited proliferation and induced apoptosis by in LNCaP and PC-3 prostate cancer cell lines

Inhibited hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT transcriptionally and posttranslationally

0.063-5 μM

[23]

Inhibited the growth of LNCaP, PC-3 and DU145 prostate cancer cells

Induced apoptosis through activation of caspases 3, 8 and 9, disruption of mitochondrial integrity, and inhibition of anti-apoptotic Bcl-2, Bcl-xL and XIAP. Induction of apoptosis was associated with the inhibition of pro-survival Akt, mTOR, NF-κB signaling proteins

1.25-20 μM

[26]

Inhibited the growth and induced apoptosis in PC-3 and C4-2 prostate cancer cells

Inhibition of p-Akt, mTOR, and NF-κB signaling proteins and their downstream targets such as p-Bad and p-Foxo3a [Akt]; p-S6K1, p-eIF-4E and p-4E-BP1 [mTOR]; and COX-2, VEGF and cyclin D1[NF-κB]

0.625-10 μM

[30]

Inhibited the growth of both K-ras mutated and wild-type K-ras pancreatic cancer cells

Inhibited of prosurvival p-Akt, NF-κB and mTOR signaling proteins and the downstream targets of Akt and mTOR, such as p-Foxo3a [Akt] and p-S6K1, p-eIF-4E and p-4E-BP1 [mTOR]

0.625- 5 μM

[32]

Inhibited the growth of colorectal cancer cells

Suppressed pro-survival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2, Bcl-xL, Bad and survivin

1.25-10 mM

[34]

Inhibited the growth of human ovarian cancer cell lines OVCAR-3, OVCAR-5 and SK-OV3 and ovarian endometrioid adenocarcinoma cell line MDAH-2774

Inhibition of Akt/ NF-κB /mTOR signaling pathway

0.625-10 μM

[36]

CDDO-Me caused the generation of ROS and pre-treatment with NAC prevented the generation of ROS in OVCAR-5 and MDA 2774 ovarian cancer cells

ROS played a pivotal role in the anti-proliferative and apoptosis-inducing activity of CDDO-Me in ovarian cancer cells

1.25–10 μM

[37]

Induced the apoptosis of glioblastoma [U87MG, U251MG] and neuroblastoma [SK-N-MC] cell lines

Inhibited the levels of anti-apoptotic and prosurvival p-Akt, NF-κB and Notch1 signaling molecules

2.5–10 μM

[38]

Reversed the resistant of paclitaxel-resistant ovarian cancer cell line OVCAR8TR and cisplatin-resistant ovarian cancer cell line A2780cp70

Inhibited IL-6 secretion, STAT3 phosphorylation, STAT3 nuclear translocation

0.3 μM

[42]

Reversed the resistant of MDR osteosarcoma cell lines KHOSR2, U-2OSTR

Inhibited STAT3 phosphorylation, STAT3 nuclear translocation and induced apoptosis

0.1; 0.3 μM

[43]

Activated the extrinsic DR-mediated apoptotic pathway in human lung cancer cells

Induced a JNK-dependent up-regulation of DR5 expression, leading to activation of caspase-8 and induction of apoptosis

0.25-1 μM

[47]

Induced JNK-dependent DR5 expression in human lung cancer cells

Depleted intracellular GSH, resulting in ER stress. Subsequently, it activated JNK, leading to CHOP-dependent DR5 up-regulation and apoptosis

0.1-2 μM

[48]

Induced apoptosis in human lung cancer cells A549 and H157

Induced apoptosis through downregulation of c-FLIP Enhanced TRAIL-induced apoptosis

0.25;0.5;1 μM

[49]

Inhibited proliferation and induced apoptosis in MiaPaCa-2 and Panc-1 human pancreatic cancer cell lines

Inhibited hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT expression and activity

1.25–5 μM

[54]

Induced apoptosis in MiaPaCa-2 and Panc-1 human pancreatic cancer cell lines

Generated ROS and inhibited the telomerase activity

1.25 μM

[55]

Inhibited MC38 colon carcinoma, Lewis lung carcinoma, and EL-4 thymoma mouse tumor lines

Blocked ROS production, decreased levels of peroxynitrite and abrogated MDSC suppressive activity against antigen-specific CD8+ T cells

>1 μM

[56]

  1. Akt: protein kinase B1;Bad: Bcl-2-associated death promoter; Bcl-2:B-cell lymphoma 2; BCL-xL: B-cell lymphoma extra large; c-FLIP: cellular FLICE inhibitory protein; CHOP: CCAAT/enhancer binding protein homologous protein; COX-2: cyclooxygenase 2; DR:death receptor; ER: endoplasmic reticulum; GSH: glutathione; hTERT: human telomerase reverse transcriptase; JNK: c-Jun NH2-terminal kinase; MDR: multidrug resistant; MDSC: myeloid-derived suppressor cells; mTOR :mammalian target of rapamycin; NAC: N-acetylcysteine; NF-κB: nuclear factor-κB; ROS: reactive oxygen species; STAT3: transcription factor signal transducers and activators of transcription 3; TRAIL :TNF related apoptosis inducing ligand; VEGF: vascular endothelial growth factor; XIAP: X-linked inhibitor of apoptosis protein.