J Korean Med Sci.  2011 Nov;26(11):1489-1494. 10.3346/jkms.2011.26.11.1489.

Apoptotic Effects of Genistein, Biochanin-A and Apigenin on LNCaP and PC-3 Cells by p21 through Transcriptional Inhibition of Polo-like Kinase-1

• Seo YJ
• Kim BS
• Chun SY
• Park YK
• Kang KS
• Kwon TG

• KMID: 1123450
• DOI: http://doi.org/10.3346/jkms.2011.26.11.1489

Abstract

Natural isoflavones and flavones are important dietary factors for prostate cancer prevention. We investigated the molecular mechanism of these compounds (genistein, biochanin-A and apigenin) in PC-3 (hormone-independent/p53 mutant type) and LNCaP (hormone-dependent/p53 wild type) prostate cancer cells. A cell growth rate and apoptotic activities were analyzed in different concentrations and exposure time to evaluate the antitumor activities of genistein, biochanin-A and apigenin. The real time PCR and Western blot analysis were performed to investigate whether the molecular mechanism of these compounds are involving the p21 and PLK-1 pathway. Apoptosis of prostate cancer cells was associated with p21 up-regulation and PLK-1 suppression. Exposure of genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells resulted in same pattern of cell cycle arrest and apoptosis. The inhibition effect for cell proliferation was slightly greater in LNCaP than PC-3 cells. In conclusion, flavonoids treatment induces up-regulation of p21 expression, and p21 inhibits transcription of PLK-1, which promotes apoptosis of cancer cells.

Keyword

Prostatic Neoplasms; Apoptosis; Flavones; Isoflavones

MeSH Terms

Antineoplastic Agents/*pharmacology
Apigenin/pharmacology
*Apoptosis
Cell Cycle/drug effects
Cell Cycle Proteins/biosynthesis/*genetics/metabolism
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21/biosynthesis/*metabolism
Flavonoids/*pharmacology
Gene Expression Regulation, Neoplastic/drug effects
Genistein/pharmacology
Humans
Male
Prostatic Neoplasms/genetics/metabolism/*pathology
Protein Kinase Inhibitors/pharmacology
Protein-Serine-Threonine Kinases/biosynthesis/*genetics/metabolism
Proto-Oncogene Proteins/biosynthesis/*genetics/metabolism
Transcription, Genetic/drug effects

Figure

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  Fig. 1 Dose dependent inhibition of cell proliferation by genistein (GEN), biochanin-A (BIO) and apigenin (Api) on LNCaP and PC-3 prostate cancer cells. The data represent mean ± SD of six independent experiments.

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  Fig. 2 Induction of apoptosis by genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells.

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  Fig. 3 Up-regulation of p21 and inhibition of PLK-1 gene expression by real-time PCR analysis treating genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells.

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  Fig. 4 p21 mediated PLK-1 protein regulation by western blot analysis treating genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells. Genistein (GEN, 100 µM), biochanin-A (BIO, 60 µM) and apigenin (API, 40 µM) were treated for 48 hr. Control cells (Ctrl) were treated with 0.1% DMSO.

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