Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo

Ming, Dong-Sheng; Pham, Steven; Deb, Subrata; Chin, Mei Yieng; Kharmate, Geetanjali; Adomat, Hans; Beheshti, Elham Hosseini; Locke, Jennifer A.; Guns, Emma Tomlinson

doi:10.1016/j.jsbmb.2014.02.006

Cited by 26 publications

(20 citation statements)

References 26 publications

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“…This result is consistent with reports that Rv1 cells can synthesize androgen (41,42) and with our profiling array data revealing regulation of steroidogenic enzymes by Siah2 (19). Restoring the expression of AKR1C3 in the Siah2 KD Rv1 cells partly rescued the AR activity and cell proliferation defects, demonstrating that AKR1C3 is a key downstream effector of Siah2.…”

Section: Discussionsupporting

confidence: 93%

The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells

Fan

Peng

Hussain

et al. 2015

Journal of Biological Chemistry

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Background: Ubiquitin ligase Siah2 promotes activity of androgen receptor (AR) in prostate cancer cells. Results:The steroidogenic enzyme AKR1C3 binds and stabilizes Siah2 by blocking Siah2 self-ubiquitination and degradation. Conclusion: We identified a catalytic independent role for AKR1C3 on AR activity via Siah2. Significance: The findings may provide new targets for development of AKR1C3 inhibitors as prostate cancer therapy.

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Section: Discussionsupporting

confidence: 93%

The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells

Fan

Peng

Hussain

et al. 2015

Journal of Biological Chemistry

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“…[48][49][50] On the other hand, it was observed that the IC 50 value on the HFB-4 normal cell line was higher by 5.7-fold and 2.6-fold compared to MCF-7 and PC-3 cancer cell lines, respectively, which might indicate the selective toxicity of PE against these cancer cells. However, the effect of PE on HepG-2 was not statistically significant when compared with its effect on HFB-4.…”

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confidence: 96%

Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study

Badawi¹,

Teaima²,

El-Say³

et al. 2018

IJN

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Background Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer activity because of its polyphenols content. The main purpose of this study was to maximize the PE chemotherapeutic efficacy by loading it in an optimized solid lipid nanoparticles (SLNs) formula. Materials and methods The influence of independent variables, which were lipid concentration (X 1 ), surfactant concentration (X 2 ) and cosurfactant concentration (X 3 ), on dependent ones, which were particle size (Y 1 ), polydispersity index (Y 2 ), zeta potential (Y 3 ), entrapment efficiency (Y 4 ) and cumulative % drug release (Y 5 ), were studied and optimized using the Box–Behnken design. Fifteen formulations of PE-SLNs were prepared using hot homogenization followed by ultra-sonication technique. Response surface plots, Pareto charts and mathematical equations were produced to study the impact of independent variables on the dependent quality parameters. The anti-proliferative activity of the optimized formula was then evaluated in three different cancer cell lines, namely, MCF-7, PC-3 and HepG-2, in addition to one normal cell line, HFB-4. Results The results demonstrated that the particle sizes ranged from 407.5 to 651.9 nm and the entrapment efficiencies ranged from 56.02 to 65.23%. Interestingly, the 50% inhibitory concentration of the optimized formula had more than a 40-fold improved effect on the cell growth inhibition in comparison with its free counterpart. Furthermore, it was more selective against cancer cells than normal cells particularly in MCF-7 breast cancer cells. Conclusion These data proved that nanoencapsulation of PE enhanced its anticancer efficacy. Therefore, our results suggested that a PE-loaded SLNs optimized-formula could be a promising chemo therapeutic agent.

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“…There are various core regulatory factors and pathways in prostate cancer associated pathways ( hsa05215 ). Steroid hormone biosynthesis has been reported to contribute to the metastasis of prostate cancer and interacts with the specific oncogene of pancreatic cancer AR , implying its core role for the prostate associated pathways that we have predicted [51, 52]. According to recent publications, such core pathway of the steroid hormone biosynthesis may also contribute to pancreatic cancer, revealing the underlying relationships between prostate cancer associated pathways (as we have predicted, hsa05215) and pancreatic cancer [53, 54].…”

Section: Resultsmentioning

confidence: 96%

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

Yin

Wang

Zhang

et al. 2016

BioMed Research International

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Pancreatic cancer is a serious disease that results in more than thirty thousand deaths around the world per year. To design effective treatments, many investigators have devoted themselves to the study of biological processes and mechanisms underlying this disease. However, it is far from complete. In this study, we tried to extract important gene ontology (GO) terms and KEGG pathways for pancreatic cancer by adopting some existing computational methods. Genes that have been validated to be related to pancreatic cancer and have not been validated were represented by features derived from GO terms and KEGG pathways using the enrichment theory. A popular feature selection method, minimum redundancy maximum relevance, was employed to analyze these features and extract important GO terms and KEGG pathways. An extensive analysis of the obtained GO terms and KEGG pathways was provided to confirm the correlations between them and pancreatic cancer.

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Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo

Cited by 26 publications

References 26 publications

The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells

The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells

Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

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