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. 2012 Feb;29(2):277-84.
doi: 10.3892/ijmm.2011.835. Epub 2011 Nov 10.

Selective Cell Cycle Arrest and Induction of Apoptosis in Human Prostate Cancer Cells by a Polyphenol-Rich Extract of Solanum Nigrum

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Selective Cell Cycle Arrest and Induction of Apoptosis in Human Prostate Cancer Cells by a Polyphenol-Rich Extract of Solanum Nigrum

Akbar Nawab et al. Int J Mol Med. .
Free PMC article

Abstract

Progression of prostate cancer is associated with escape of tumor cells from cell cycle arrest and apoptosis. Agents capable of selectively eliminating cancer cells by cell cycle arrest and/or induction of apoptosis offer a highly desirable approach. Here we demonstrate that a polyphenolic extract derived from ripe berries of Solanum nigrum (SN) differentially causes cell cycle arrest and apoptosis in various human prostate cancer cells without affecting normal prostate epithelial cells. Virally transformed normal human prostate epithelial PZ-HPV-7 cells and their cancer counterpart CA-HPV-10 cells, were used to evaluate the growth-inhibitory effects of the SN extract. SN treatment (5-20 µg/ml) of PZ-HPV-7 cells resulted in growth inhibitory responses of low magnitude. In sharp contrast, SN treatment of CA-HPV-10 cells increased cytotoxicity, decreased cell viability and induced apoptosis. Similar results were noted in the human prostate cancer LNCaP, 22Rv1, DU145 and PC-3 cell lines, where significant reductions in cell viability and induction of apoptosis was observed in all these cells, an effect independent of disease stage and androgen association. Cell cycle analysis revealed that SN treatment (5-20 µg/ml) resulted in a dose-dependent G2/M phase arrest and subG1 accumulation in the CA-HPV-10 but not in the PZ-HPV-7 cell line. Our results, for the first time, demonstrate that the SN extract is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. SN may be developed as a promising therapeutic and/or preventive agent against prostate cancer.

Figures

Figure 1
Figure 1
(A) UV spectrum of aqueous berry extract of Solanum nigrum (SN). The scan was obtained from 200–750 nm and then subjected to absorbance at 750 nm using gallic acid as standard. (B) HPLC chromatogram of an aqueous SN extract demonstrating the presence of various polyphenolic constituents. (C) Electrospray product ion mass spectra of SN extract. The ion chromatograms were extracted at m/z corresponding to the molecular mass and structure of various polyphenolic compounds were detected. The details are described in the Materials and methods section.
Figure 2
Figure 2
(A) Effect of SN extract on cell viability in non-cancerous PZ-HPV-7 cells, and their cancer counterpart CA-HPV-10 cells. The cells were exposed to the specified concentration of SN extract for 24 h, and viability of the cells was determined by the MTT assay. Cell viabilities are depicted as percentages; vehicle-treated cells were regarded as 100% viable. The data represent the mean of 3 experiments performed in triplicate. (B) Light microscopy images of virally transformed normal human prostate epithelial PZ-HPV-7 cells and their cancer counterpart CA-HPV-10 cells treated with aqueous SN extract. Treatment of CA-HPV-10 cells with SN extract exhibits morphological changes consistent with apoptosis, whereas no such morphological changes were observed in PZ-HPV-7 cells. (C) DNA fragmentation by SN extract in CA-HPV-10 cells. The cells were treated with 5–20 μg/ml concentration of SN and 48 h later, the cells were collected, DNA was isolated and subjected to agarose gel electrophoresis, followed by visualization of bands under UV light. The PZ-HPV-7 cells did not indicate DNA fragmentation by SN extract. The details are described in the Materials and methods section.
Figure 3
Figure 3
Effect of SN extract on induction of apoptosis in virally-transformed normal human prostate epithelial PZ-HPV-7 cells, and their cancer counterpart CA-HPV-10 cells. The cells were treated with 5–20 μg/ml concentration of SN extract for 48 h and the number of cells undergoing apoptosis was determined using the TUNEL assay. Details are described in the Materials and methods section.
Figure 4
Figure 4
Effect of SN extract on DNA cell cycle in non-cancerous PZ-HPV-7 cells, and their cancer counterpart CA-HPV-10 cells. Log phase growing cells were exposed to increasing concentrations of SN extract (5–20 μg/ml) in complete medium for 24 h, stained with PI (50 mg/ml) and analyzed by flow cytometry. Percentages of cells in subG1, G0/G1, S and G2/M phase were calculated using Cell Quest and ModFit cell cycle analysis software, represented in the right side of the histogram. Data shown here are from a representative experiment repeated three times with similar results. The details are described in the Materials and methods section.
Figure 5
Figure 5
Effect of SN extract on cell viability and induction of apoptosis in human prostate cancer 22Rv1, LNCaP, DU145 and PC-3 cells. (A) The cells were exposed to 5–20 μg/ml concentration of SN extract for 24 h, and viability of the cells was determined by the MTT assay. Cell viabilities are depicted as percentages; vehicle-treated cells were regarded as 100% viable. The values represent mean ± SD of three different assays in duplicate; *P<0.05; **P<0.001, compared to control. (B) DNA fragmentation assay. The cells were treated with vehicle or 5–20 μg/ml concentration of SN extract for 48 h, collected for DNA isolation and subjected to agarose gel electrophoresis, followed by visualization of bands under UV light. All prostate cancer cells underwent DNA fragmentation by the SN extract. Details are described in the Materials and methods section.

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