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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+&+Vi ... ctID=20283
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What's the verdict on licorice?
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+&+Vi ... ctID=20283
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What's the verdict on licorice?