Introduction
Introduction of CDDO-Me
In vivo cancer preventive effects of CDDO-Me
Effects | Mechanisms | Dose/duration | Route | Reference |
---|---|---|---|---|
Decreased the average tumor burden of vinyl carbamate-induced andenocarcinoma in female A/J mice | Suppression of the ability of IFN-γ to induce de novo formation of NO synthase; Induction of HO-1; Suppression of phosphorylation of STAT3 as well as induction of apoptosis | 60 mg/kg, 2 weeks | Diet | [16] |
Prevented the formation of ER- negative mammary tumors in the mouse mammary tumor virus-neu transgenic model | Inhibited constitutive STAT3 phosphorylation and the degradation of IKBα | 60 mg/kg, 45 weeks | Diet | [17] |
Increased survival of the KPC mice by 3 to 4 weeks | Interacted with both STAT3 and IKK to decrease constitutive IL-6 secretion, inhibited constitutive STAT3 phosphorylation, and blocked the degradation of IKBα when challenged with TNF-α | 60 mg/kg diet or 15 mg/kg body weight. Beginning at 4 weeks of age until detect tumor | Diet | [18] |
Delayed ER–negative mammary carcinogenesis in polyoma middle T Mice | Inhibited cyclin D1 and decreased phosphorylation of EGFR and STAT3 | 50 mg/kg, 4–8 weeks | Diet | [19] |
Delayed tumor development in the BRCA1-mutated mice by an average of 5.2 weeks | Interacted with ErbB2, decreased constitutive phosphorylation of ErbB2, inhibited proliferation, and induced G0/G1 arrest | 50 mg/kg. Beginning at 12 weeks of age until detect tumor | Diet | [20] |
Inhibited the progression of preneoplastic lesions in the DLP and VP lobes to adenocarcinoma in TRAMP mice | Inhibited cell proliferation, reduced the density of blood vessels and promoted apoptosis in the prostatic tissue | 10 μmol/kg. 20 weeks | Oral gavage | [21] |
Inhibited the progression of the preneoplastic lesions to adenocarcinoma in the DLP and VP lobes of TRAMP mice | Inhibited the expression of prosurvival p-Akt and NF-κB in the prostate | 7.5 mg/kg/day, 5 days/week. Early intervention initiated at five weeks of age for 20 weeks. Delayed administration started at 12 week of age for 12 weeks | Oral gavage | [22] |
Inhibited the progression of preneoplastic lesions to adenocarcinoma of the prostate in TRAMP mice | Decreased TERT and its regulatory proteins in the prostate | 15 μmol/kg/day, 5 days/week, 20 weeks | Oral gavage | [23] |
In vitro and in vivo anticancer effects of CDDO-me
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] |