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Chinese red yeast rice extract inhibits androgen‐dependent and –independent prostate cancer cell growth but by different mechanisms
Author(s) -
Hong Mee Young,
Seeram Navindra,
Zhang Yanjun,
Heber David
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a364-c
Subject(s) - lncap , prostate cancer , cell growth , endocrinology , cancer research , medicine , apoptosis , viability assay , cancer cell , biology , cell , chemistry , cancer , biochemistry
Early prostate cancer is androgen‐dependent (AD), but in later stages of the disease androgen‐independent (AI) tumors arise with an eventual fatal outcome. RYR contains monacolin K (MK) which is identical to lovastatin, with the ability to inhibit cholesterol synthesis. Since increased cholesterol level in prostate tissues is correlated with its malignancy, we hypothesized that RYR may protect against prostate cancer by inhibiting cancer cell growth via downregulation of de novo cholesterogenesis. Two human prostate cancer cell lines, either AD (LNCaP) or AI (LNCaP‐AR), were treated with RYR or MK‐free RYR. Cell proliferation and apoptosis were determined using the Cell Titer‐Glo Luminescent viability assay and Cell Death Detection ELISA assay, respectively. Transcription levels of 3‐hydroxy‐3‐methyl‐glutaryl CoA reductase (HMGCR) and sterol response element binding protein‐2 (SREBP‐2) were determined by real time PCR. RYR inhibited cell proliferation in both prostate cancer cell lines (p<0.001) and stimulated apoptosis only in LNCaP cells (p<0.01). MK‐free RYR showed similar results as the RYR treatment. Mevalonate (end product of HMGCR) treatment reversed the RYR's anti‐proliferative in LNCaP‐AR cells but not in LNCaP cells. RYR increased mRNA expression of HMGCR and SREBP‐2 (p<0.01) but MK‐free RYR decreased expression in both cell lines (p<0.01). This study demonstrated that RYR inhibits cancer cell growth due to its MK component in AI prostate cancer cells, while via its other constituents and MK in AD cells. Funds: UCLA CNRU CA 42710 and DOD CDMRP PC060044.