General Information:

Id: 5,265 (click here to show other Interactions for entry)
Diseases: Cancer
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Homo sapiens
article
Reference: Choi H et al.(2008) Curcumin attenuates cytochrome P450 induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by ROS-dependently degrading AhR and ARNT Cancer Sci. 99: 2518-2524 [PMID: 19018768]

Interaction Information:

Comment TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental contaminant. When exposed to TCDD, mammalian cells undergo malignant transformation via abnormal intracellular signaling cascades, and the robust inductions of cytochrome P450 (CYP) enzymes are considered to mediate carcinogenesis by producing genotoxic metabolites. This study examined whether curcumin has preventive activity against TCDD-induced CYP production and cell transformation. The cellular levels of cytochrome P450 (CYP) 1A1 and 1B1 were examined, because these are known to generate estrogen metabolites that mediate genotoxic stress. In Hep3B (hepatoma) and MCF7 (mammary carcinoma) cells curcumin inhibited CYP1A1 and 1B1 induction by TCDD at the mRNA and protein levels.
Formal Description
Interaction-ID: 51316

drug/chemical compound

Curcumin

decreases_expression of

gene/protein

CYP1A1

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells; if expression was induced by dioxin
Comment TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental contaminant. When exposed to TCDD, mammalian cells undergo malignant transformation via abnormal intracellular signaling cascades, and the robust inductions of cytochrome P450 (CYP) enzymes are considered to mediate carcinogenesis by producing genotoxic metabolites. This study examined whether curcumin has preventive activity against TCDD-induced CYP production and cell transformation. The cellular levels of cytochrome P450 (CYP) 1A1 and 1B1 were examined, because these are known to generate estrogen metabolites that mediate genotoxic stress. In Hep3B (hepatoma) and MCF7 (mammary carcinoma) cells curcumin inhibited CYP1A1 and 1B1 induction by TCDD at the mRNA and protein levels.
Formal Description
Interaction-ID: 51320

drug/chemical compound

Curcumin

decreases_expression of

gene/protein

CYP1B1

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells; if expression was induced by dioxin
Comment To investigate the mechanism by which curcumin inhibits the XRE binding of AhR, AhR and ARNT levels in total cell lysates were analyzed. ARNT levels were reduced during curcumin treatment, but AhR was also down-regulated by curcumin. In nuclear fractions, AhR and ARNT levels were found to be enhanced by TCDD, whereas their total levels were not significantly altered. This suggests that AhR is activated by TCDD and that it is then translocated to the nucleus with ARNT. Furthermore, curcum in noticeably reduced nuclear AhR and ARNT levels in TCDD-treated cells, but not their cytosolic levels.
Formal Description
Interaction-ID: 51322

drug/chemical compound

Curcumin

decreases_quantity of

gene/protein

ARNT

in Hep3B hepatic cancer cells
Comment To investigate the mechanism by which curcumin inhibits the XRE binding of AhR, AhR and ARNT levels in total cell lysates were analyzed. ARNT levels were reduced during curcumin treatment, but AhR was also down-regulated by curcumin. In nuclear fractions, AhR and ARNT levels were found to be enhanced by TCDD, whereas their total levels were not significantly altered. This suggests that AhR is activated by TCDD and that it is then translocated to the nucleus with ARNT. Furthermore, curcum in noticeably reduced nuclear AhR and ARNT levels in TCDD-treated cells, but not their cytosolic levels.
Formal Description
Interaction-ID: 51328

drug/chemical compound

Curcumin

decreases_quantity of

gene/protein

AHR

in Hep3B hepatic cancer cells
Drugbank entries Show/Hide entries for AHR
Comment To investigate the mechanism by which curcumin inhibits the XRE binding of AhR, AhR and ARNT levels in total cell lysates were analyzed. ARNT levels were reduced during curcumin treatment, but AhR was also down-regulated by curcumin. In nuclear fractions, AhR and ARNT levels were found to be enhanced by TCDD, whereas their total levels were not significantly altered. This suggests that AhR is activated by TCDD and that it is then translocated to the nucleus with ARNT. Furthermore, curcum in noticeably reduced nuclear AhR and ARNT levels in TCDD-treated cells, but not their cytosolic levels.
Formal Description
Interaction-ID: 51331

drug/chemical compound

Curcumin

decreases_activity of

gene/protein

AHR

in Hep3B hepatic cancer cells; via inhibition of dioxin-induced translocation into the nucleus
Drugbank entries Show/Hide entries for AHR
Comment To investigate the mechanism by which curcumin inhibits the XRE binding of AhR, AhR and ARNT levels in total cell lysates were analyzed. ARNT levels were reduced during curcumin treatment, but AhR was also down-regulated by curcumin. In nuclear fractions, AhR and ARNT levels were found to be enhanced by TCDD, whereas their total levels were not significantly altered. This suggests that AhR is activated by TCDD and that it is then translocated to the nucleus with ARNT. Furthermore, curcum in noticeably reduced nuclear AhR and ARNT levels in TCDD-treated cells, but not their cytosolic levels.
Formal Description
Interaction-ID: 51333

drug/chemical compound

Curcumin

decreases_activity of

gene/protein

ARNT

in Hep3B hepatic cancer cells; via inhibition of dioxin-induced translocation into the nucleus
Comment Previous studies demonstrated that oxidative stress facilitates the proteasomal degradation of ARNT. This study demonstrated that curcumin induced the proteasomal degradations of AhR and ARNT by increasing oxidative stress and subsequently abolished the TCDD-induced expressions of CYP1A1 and CYP1B1.
Formal Description
Interaction-ID: 51334

drug/chemical compound

Curcumin

increases_activity of

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells; via increased oxidative stress
Comment Previous studies demonstrated that oxidative stress facilitates the proteasomal degradation of ARNT. This study demonstrated that curcumin induced the proteasomal degradations of AhR and ARNT by increasing oxidative stress and subsequently abolished the TCDD-induced expressions of CYP1A1 and CYP1B1.
Formal Description
Interaction-ID: 51342

drug/chemical compound

Curcumin

increases_activity of

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells
Comment Intracellular reactive oxygen species (ROS) levels noticeably increased in curcumin-treated MCF-7 or Hep3B cells versus untreated cells.
Formal Description
Interaction-ID: 51344

drug/chemical compound

Curcumin

increases_quantity of

drug/chemical compound

Reactive oxygen species

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells
Comment The results suggest that curcumin degrades AhR and ARNT redox-dependently through proteasomes, and that this impairs xenobiotic responses to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin).
Formal Description
Interaction-ID: 51345

drug/chemical compound

Curcumin

decreases_activity of

drug/chemical compound

2,3,7,8-Tetrachlorodibenzodioxin

in MCF-7 breast cancer cells, in Hep3B hepatic cancer cells
Comment Curcumin prevented non-cancerous cells from being transformed to cancerous cells as characterized by cell density- and anchorage-independent proliferation.
Formal Description
Interaction-ID: 51350

drug/chemical compound

Curcumin

decreases_activity of

phenotype

tumorigenesis

in PNT2 prostate cells, in HEK293 cells; if induced by dioxin