Botanical COX inhibitor, Isoliquiritigenin, down regulates androgen-receptor and PSA proteins

Botanical COX inhibitor, Isoliquiritigenin, down regulates androgen-receptor and PSA proteins

Botanical COX inhibitor, Isoliquiritigenin, down regulates androgen-receptor and PSA proteins
Background: Isoliquiritigenin (ISL) is a flavonoids isolated from the licorice root, an herb frequently used in traditional Chinese medicine. In investigating flavonoids, we found that ISL suppresses growth of both androgen receptor (AR) positive (LNCaP) and negative prostate cancer cell lines (DU-145) in a manner different from other phytoestrogens. We thus set out to investigate the specific molecular action of ISL on prostate cancer cells. Methods: HPLC was employed to isolate ISL. MTT cell viability assay was used to evaluate the anti-proliferative activity of ISL towards LNCaP and DU-145. Fluorescence microscopy (FM) was used to observe the morphology of the cells. To further understand the mechanism of action, flow cytometric and Western blot analyses were employed to investigate the effect on cell cycle and protein levels of the androgen receptor (AR) and prostate specific antigen (PSA). Enzyme immunoassay (EIA) was used to determine the inhibitory activity against cyclooxgenase (COX1,2). Results: ISL exhibited potent activity in inhibiting prostate cancer cell proliferation. The 50% inhibitory concentration (IC50) determined by MTT was 23.3 ±3.4 and 15.7±2.9 µM for LNCaP and DU-145 respectively. FM examination revealed an increased frequency of apoptosis in both cell lines. At concentrations comparable to the IC50 the flow cytometric data showed that ISL induced a G1 phase arrest in LNCaP, while it blocked the cell cycle at G2M phase in DU-145 cells. Western blot analysis further revealed ISL caused a down regulation of AR and PSA (both intracellular and secreted) protein levels. The anti-inflammatory property of ISL was found to be directly associated with its strong inhibition of the COX -1,2 activity, with an IC50 of 10.6 µM for COX-2. Conclusions: Our study shows ISL is a COX inhibitor and down regulates AR and PSA proteins, a result consistent with other findings on the action of COX-2 inhibitors. Since DU-145 does not express AR nor COX-2, it is likely ISL involves other molecular targets as well. Further study is needed.

http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=37&abstractID=20283

-----------

What do you guys think?

Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells.

Isoliquiritigenin (ILTG) is a flavonoid with chalcone structure (4,2',4'-trihydroxychalcone), an active component present in plants like Glycyrrhiza and Dalbergia which showed various biological activities including anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to the underlying mechanism involved in explaining the various activities of the compound, we carried out a detailed study on the effect of ILTG on the expression of cell adhesion molecules on human primary endothelial cells. We demonstrate here that ILTG inhibits TNF-alpha induced adhesion of neutrophils to endothelial monolayer by blocking the expression of ICAM-1, VCAM-1 and E-selectin. Since NF-kappaB is a major transcription factor involved in the transcriptional regulation of cell adhesion molecules, thus we studied the status of NF-kappaB activation in ILTG treated endothelial cells. We demonstrate that ILTG inhibits the translocation and activation of nuclear factor-kappaB (NF-kappaB) by blocking the phosphorylation and subsequent degradation of IkappaBalpha. As oxidative stress is also known to regulate the activation of NF-kappaB to modulate TNF-alpha signaling cascade, we tested the effect of ILTG on reactive oxygen species (ROS). We found that it inhibits TNF-alpha induced ROS production in endothelial cells. These results have important implications for using ILTG or its derivatives towards the development of effective anti-inflammatory molecules.

CS.....?

Misirlou - chore did another thread on it, but I missed this one. Isoliquiritigenin looks promising.

https://immortalhair.forumotion.com/natural-hair-regrowth-forum-f1/botanical-cox-inhibitor-isoliquiritigenin-down-regulates-androgen-receptor-and-psa-proteins-t1874.htm

It seems licorice has this but if one wanted a pure form of this flavanoid ... where would one get it?

Thanks