Aryl Hydrocarbon

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by tundesmith
Last updated 5 years ago

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Science
Subject:
Experiments

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Aryl Hydrocarbon

Curcumin Inhibits Aryl Hydrocarbon Receptor Signaling in Advanced Prostate Cancer Cells

BACKGROUND

Prostate Cancer is a very serious disease, and according to the American Cancer Society it is the second most common cancer and the second leading cause of cancer death in American men behind lung cancer. Curcumin is a phytochemical with many different molecular targets. It has been shown to induce apoptosis incancer cells and other anti-carcinogenic properties through many different pathways, one being the AhR Pathway.AhR is a transcription factor that elicits the effects of a wide range of environmental toxins, binding to not only natural phytochemicals, but also to dioxins such as benzo-a-pyrene or 2,3,7,8 tetrachloro-dibenzo-dioxin (TCDD) found in cigarette smoke and barbecued foods, that can damage the immune system and also cause cancer.

Objective: The goal of this study is to determine if AhR expression is required for the apoptotic effects of curcumin in DU145 cells. Methods: DU145 cells with shRNA-mediated depletion of the AhR protein expression (-AhR) and a scrambled vector control (Scr) were treated with increasing concentrations of curcumin. Cell viability for each concentration was assessed at 1, 3, 6, 12, 18 and 24 hours in both DU145 (-AhR) and (Scr) cells. Results: Modulation of cell viability by curcumin correlated with AhR expression. DU145 (SCR) cells responded to lower doses of curcumin at earlier time points compared to the (-AhR) cells. Conclusion: The results suggest that curcumin may illicit anti-apoptotic effects through modulation of the AhR pathway. Furthermore, curcumin may be selective to advanced prostate cancer.

CURCUMIN INHIBITS AHR ACTIVITY

AHR EXPRESSION IN PROSTATE CANCER CELL LINES

CURCUMIN MAY ILLICIT ANTI-APOPTOTIC EFFECTS

MODULATION OF CELL VIABILITY BY CURCUMIN

ACKNOWLEDGEMENTS

In the picture to the left, Curcumin inhibits TCDD induced transformation of AhR and expression of CYP1A1. In the picture on the right, Curcumin is shown to inhibit transformation of aryl hydrocarbon receptor through its phosphorylation.

Thank you to Dr. Joann Powell and Stanley Williams for their mentorship. The Dr. John H. Hopps Research Defense Scholars Program for their support and funding. This work was funded by Grant # 8 G12 MD007590-NIH/NIMHD, Grant # 2G12RR003062-22.

Western Blots confirm Advanced PCa cell models express increase in AhR protein in comparison to the androgen-sensitive LNCaP cell model and confirms shRNA mediated depletion of AhR protein in DU145 cells (-AhR) compared to DU145 scrambled vector control cells (SCR).

Q-PCR Analysis compares CYP1B1 fold change between DU145 -AhR cells and DU145 scrambled vector control cells after being treated with curcumin. At 1 uM and 10 uM of added curcumin there are significant changes in the level of CYP1B1 fold change between the two cell lines.

DU145 scrambled control vector cells and DU145 -AhR cells were treated with increasing concentrations of curcumin. Cell viability for each concentration was assessed at 1, 3, 6, 12, 18 and 24 hours. The results suggest that modulation of cell viability by curcumin is AhR dependent. Furthermore, the apoptotic effects of curcumin may be selective to advanced prostate cancer cells that over-express AhR.

Tunde SmithJoann Powell, PhD CBIO480 Nathan Bowen, PhDFinal Presentation


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