Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells
Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechani...
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MDPI AG
2020-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/8/282 |
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| author | Neelu Batra Anhao Sam Tibebe Woldemariam George Talbott Ralph W. de Vere White Paramita M. Ghosh Nilesh W. Gaikwad Simeon O. Kotchoni Ruth L. Vinall |
| author_facet | Neelu Batra Anhao Sam Tibebe Woldemariam George Talbott Ralph W. de Vere White Paramita M. Ghosh Nilesh W. Gaikwad Simeon O. Kotchoni Ruth L. Vinall |
| author_sort | Neelu Batra |
| collection | DOAJ |
| description | Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (<i>p</i> < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (<i>p</i> < 0.001), 17βHSD (<i>p</i> < 0.001), CYP17A (<i>p</i> < 0.01), SRB1 (<i>p</i> < 0.0001), and StAR (<i>p</i> < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (<i>p</i> < 0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (<i>p</i> < 0.001) and 1.5-fold decrease (<i>p</i> < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted. |
| first_indexed | 2024-03-10T17:38:26Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T17:38:26Z |
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| spelling | doaj.art-42072152442f47438c7a4e3958c40b692023-11-20T09:46:24ZengMDPI AGBiomedicines2227-90592020-08-018828210.3390/biomedicines8080282Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer CellsNeelu Batra0Anhao Sam1Tibebe Woldemariam2George Talbott3Ralph W. de Vere White4Paramita M. Ghosh5Nilesh W. Gaikwad6Simeon O. Kotchoni7Ruth L. Vinall8Department of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USAUC Davis Comprehensive Cancer Center, UC Davis, Sacramento, CA 95817, USADepartment of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USAGaikwad Steroidomics Laboratory, LLC, Davis, CA 95616, USADepartment of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USADepartment of Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USAOur group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (<i>p</i> < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (<i>p</i> < 0.001), 17βHSD (<i>p</i> < 0.001), CYP17A (<i>p</i> < 0.01), SRB1 (<i>p</i> < 0.0001), and StAR (<i>p</i> < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (<i>p</i> < 0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (<i>p</i> < 0.001) and 1.5-fold decrease (<i>p</i> < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted.https://www.mdpi.com/2227-9059/8/8/282prostate cancerIntracrine androgen synthesisCYP17genistein combined polysaccharideGenistein |
| spellingShingle | Neelu Batra Anhao Sam Tibebe Woldemariam George Talbott Ralph W. de Vere White Paramita M. Ghosh Nilesh W. Gaikwad Simeon O. Kotchoni Ruth L. Vinall Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells Biomedicines prostate cancer Intracrine androgen synthesis CYP17 genistein combined polysaccharide Genistein |
| title | Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells |
| title_full | Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells |
| title_fullStr | Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells |
| title_full_unstemmed | Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells |
| title_short | Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells |
| title_sort | genistein combined polysaccharide gcp can inhibit intracrine androgen synthesis in prostate cancer cells |
| topic | prostate cancer Intracrine androgen synthesis CYP17 genistein combined polysaccharide Genistein |
| url | https://www.mdpi.com/2227-9059/8/8/282 |
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