Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer

Alipour, Ahmad; Alidoosti, A.; Hosseini, Y.; Parvin, Mahmoud; Emranpour, Mohammad Hasan; Taslimi, F; Salehi, Ensieh; Fadavi, Pedram

doi:10.1007/s11670-011-0306-x

Cited by 27 publications

(28 citation statements)

References 32 publications

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“…In our study, AA can also down-regulate AR through supressing p300. Androgen is involved in cell cycle progression at G1/S transition and androgen depletion of LNCaP cells resulted in G1 arrest of the cell cycle with suppression of cyclin D1 expression and CDK4 activity (17). Androgen plays a key role in the development of prostate cancer through AR signaling.…”

Section: Discussionmentioning

confidence: 99%

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Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Jing¹,

Tan²,

Binghai³

et al. 2012

Chin. J. Cancer Res.

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Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. It is widely regarded as a non-specific histone acetyltransferase inhibitor of p300. The effects and the mechanisms of AA in LNCaP cells (prostate cancer cells) remain unknown. To investigate the effect of AA on LNCaP cells, we had carried out several experiments and found that AA inhibits LNCaP cell proliferation, induces G1/S cell cycle arrest and apoptosis of LNCaP cell. The mechanisms via which AA acts on LNCaP cells may be due to the following aspects. First, AA can regulate p300 transcription and protein level except for its mechanisms regulating function of p300 through post-translational modification in LNCaP cells. Second, AA can activate p53 through increasing the phosphorylation of p53 on Ser15 in LNCaP cells. AA can selectively activate p21 (target genes of p53). Third, AA can down-regulates androgen receptor (AR) through supressing p300. Our study suggests that AA has multiple anti-tumor activities in LNCaP cells and warrants further investigation. Chin J Cancer Res 2012;24(4):275-283 www.thecjcr.org culture medium when necessary. DMEM, growth factorreduced matrigel and fetalbovine serum (FBS) were bought from BD Corporation (San Jose, CA). The Lipofectamine™ 2000 and the Total RNA Extraction kit were purchased from Invitrogen (Carlsbad, CA). The MTT Cell Proliferation and Cytotoxicity Assay kit and the Annexin V-FITC & PI Apoptosis Detection kit were purchased from KeyGen Biotech (Nanjing, China). SYBR Green PCR Master Mix were purchased from Fermentas (Burlington, Ontario, Canada). The Total Protein Extraction kit was purchased from ProMab (Changsha, China). Primary antibodies for p300, p21, p53, AR, cyclin D1 and siRNA specifically for p300 were bought from Santa Cruz Biotechnology (Santa Cruz, CA). Primary antibody for phospho-p53 (Ser 15) was purchased from Cell Signaling Technology. RPMI 1640 was purchased from GIBCO. Cell lines and cell cultureLNCaP was purchased from Yinrun (Changsha, China). LNCaP is a classical metastatic prostate adenocarcinoma cell line, derived from metastatic lymph nodes. LNCaP was cultured with both RPMI 1640 and 10% FBS, and subcultured weekly (37 ℃, 5% CO 2 ). p300 siRNA transfectionT h e L n c a p c e l l s w e r e s e e d e d i n t o 6 -w e l l p l a t e s (4×10 4 -5×10 4 cells/well) and cultured in 2 mL basic culture medium containing 10% FBS overnight until the cells were 70% confluent. Cells were transiently transfected with a validated scrambled control siRNA, or p300 siRNA by using InterferinTM transfection reagent. The mixture of siRNA and InterferinTM transfection reagent was incubated for 10 min, added to each well of the 6-well plates and incubated at 37 ℃ for 24 h before drug treatment. Detecting the inhibition of cell growth using MTT assaysLncap cells were treated with AA or transfected with p300 siRNA before drug treatment. Cells were incubated at various concentrations (0, 5, 25, and 125 μmol/L) at a series of time points (0, 4, 24 and 28 h). Then, 5 mg/mL of MTT so...

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Section: Discussionmentioning

confidence: 99%

“…Androgen is an important biological effector of prostate cancer progression (17). Many studies have demonstrated that phytochemicals can effectively inhibit the apoptosis and proliferation of prostate cancer cells (18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Jing¹,

Tan²,

Binghai³

et al. 2012

Chin. J. Cancer Res.

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“…This alteration has been detected in many studies [25, 28, 34, 38], although some have reported controversial results [27, 29, 36]. Cho, NY et al [26].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis

Dou

Zhou

Fan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Retinoic acid receptor beta (RAR beta) is a retinoic acid receptor gene that has been shown to play key roles during multiple cancer processes, including cell proliferation, apoptosis, migration and invasion. Numerous studies have found that methylation of the RAR beta promoter contributed to the occurrence and development of malignant tumors. However, the connection between RAR beta promoter methylation and prostate cancer (PCa) remains unknown. This meta-analysis evaluated the clinical significance of RAR beta promoter methylation in PCa. Materials and Methods: We searched all published records relevant to RAR beta and PCa in a series of databases, including PubMed, Embase, Cochrane Library, ISI Web of Science and CNKI. The rates of RAR beta promoter methylation in the PCa and control groups (including benign prostatic hyperplasia and normal prostate tissues) were summarized. In addition, we evaluated the source region of available samples and the methods used to detect methylation. To compare the incidence and variation in RAR beta promoter methylation in PCa and non-PCa tissues, the odds ratio (OR) and 95% confidence interval (CI) were calculated accordingly. All the data were analyzed with the statistical software STATA 12.0. Results: Based on the inclusion and exclusion criteria, 15 articles assessing 1,339 samples were further analyzed. These data showed that the RAR beta promoter methylation rates in PCa tissues were significantly higher than the rates in the non-PCa group (OR=21.65, 95% CI: 9.27-50.57). Subgroup analysis according to the source region of samples showed that heterogeneity in Asia was small (I²=0.0%, P=0.430). Additional subgroup analysis based on the method used to detect RAR beta promoter methylation showed that the heterogeneity detected by MSP (methylation-specific PCR) was relatively small (I²=11.3%, P=0.343). Conclusion: Although studies reported different rates for RAR beta promoter methylation in PCa tissues, the total analysis demonstrated that RAR beta promoter methylation may be correlated with PCa carcinogenesis and that the RAR beta gene is particularly susceptible. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic utility of RAR beta promoter methylation in PCa.

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“…Reactivation of p16 INK4a will likely be of clinical benefit to cancer patients as its expression has been associated with longer disease-free survival and better prognosis in human breast cancer (35). In addition, the prognostic value of determining p16 INK4a promoter methylation has been reported for breast (7) and prostate cancers (8). Further in vivo studies are needed to evaluate the possible benefits of combining EGCG with a clinically useful HDAC inhibitor, such as suberoylanilide hydroxamic acid.…”

Section: Discussionmentioning

confidence: 99%

“…Methylation of p16 INK4a may be an early event in carcinogenesis (7). Further more, the detection of p16 INK4a hypermethylation at higher concentrations in the plasma of breast cancer patients than in healthy control patients suggests that it may be a suitable tool for cancer screening, and its prognostic value has been suggested for breast and prostate cancer patients (7,8).…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a

Shen

et al. 2013

Oncology Reports

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DNA methylation and histone deacetylation play important roles in the occurrence and development of cancers by inactivating the expression of tumor suppressors, including p16(INK4a), a cyclin-dependent kinase inhibitor. The present study investigated the effect of epigallocatechin-3-gallate (EGCG) alone or in combination with trichostatin A (TSA) on p16(INK4a) gene expression and growth in human malignant lymphoma CA46 cells. CA46 cell viability and cell cycle were analyzed; methylation of the p16(INK4a) gene was assessed by nested methylation-specific PCR (n-MSP). p16(INK4a )mRNA and protein expression was determined by real-time quantitative PCR and western blot analyses, respectively. Both EGCG and TSA alone inhibited CA46 cell proliferation; the combined treatment (6 µg/ml EGCG and 15 ng/ml TSA) significantly reduced CA46 cell proliferation from 24 to 96 h (all P<0.001). Cells treated with 24 µg/ml EGCG or the combination treatment (6 µg/ml EGCG and 15 ng/ml TSA) had lower proliferative indices when compared to the other groups. Co-treatment with EGCG and TSA decreased p16(INK4a) gene methylation, which coincided with increased p16(INK4a) mRNA and protein expression. Thus, EGCG and TSA synergistically reactivate p16(INK4a) gene expression in part through reducing promoter methylation, which may decrease CA46 cell proliferation.

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Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer

Cited by 27 publications

References 32 publications

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis

Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a

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