Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms

Estrogens are hormones that have been extensively presented in many types of cancer such as breast, uterus, colorectal, prostate, and others, due to dynamically integrated signaling cascades that coordinate cellular growth, differentiation, and death which can be potentially new therapeutic targets. Despite the historical use of estrogens in the pathogenesis of prostate cancer (PCa), their biological effect is not well known, nor their role in carcinogenesis or the mechanisms used to carry their therapeutic effects of neoplastic in prostate transformation. The expression and regulation of the estrogen receptors (ERs) ERα, ERβ, and GPER stimulated by agonists and antagonists, and related to prostate cancer cells are herein reviewed. Subsequently, the structures of the ERs and their splice variants, the binding of ligands to ERs, and the effect on PCa are provided. Finally, we also assessed the contribution of molecular simulation which can help us to search and predict potential estrogenic activities.

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Molecular Mechanisms of Essential Fatty Acids and Metabolites in Regulation of Prostate Cancer Cells

10.21236/ada425113 ◽

2004 ◽

Author(s):

Charles Y. Young

Keyword(s):

Prostate Cancer ◽

Fatty Acids ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Essential Fatty Acids ◽

Prostate Cancer Cells

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Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

Bone Research ◽

10.1038/s41413-021-00136-2 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Navatha Shree Polavaram ◽

Samikshan Dutta ◽

Ridwan Islam ◽

Arup K. Bag ◽

Sohini Roy ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Osteoclast Differentiation ◽

Potential Effect ◽

Tumor Burden ◽

Bone Lesions ◽

Prostate Cancer Cells

AbstractUnderstanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

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Newly synthesized benzimidazoles inhibits vascular endothelial growth factor and matrix metalloproteinase-2 and -9 levels in prostate cancer cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210924114856 ◽

2021 ◽

Vol 21 ◽

Author(s):

Suleyman Ilhan ◽

Gamze Dilekci ◽

Adem Guner ◽

Hakan Bektas

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Umbilical Vein ◽

Imidazole Ring ◽

Matrix Metalloproteinase 2 ◽

Benzimidazole Derivatives ◽

Prostate Cancer Cells ◽

Protein Levels ◽

Umbilical Vein Endothelial Cells

Background: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. Objective: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the possible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). Methods: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. Results: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. Conclusion: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment.

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