Novel daidzein molecules exhibited anti-prostate cancer activity through nuclear receptor ERβ modulation, in vitro and in vivo studies

2021 ◽  
pp. 1-13
Author(s):  
R. Ranjithkumar ◽  
K. Saravanan ◽  
B. Balaji ◽  
S. Hima ◽  
S. Sreeja ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptor ◽  
In Vivo Studies ◽  
Cancer Activity

scholarly journals Vitamin D and prostate cancer

2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Physiological Role ◽  
In Vivo Studies ◽  
Vitamin D Metabolism ◽  
Genetic Changes ◽  
Metabolic Role

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.

scholarly journals A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Komakech ◽  
Youngmin Kang ◽  
Jun-Hwan Lee ◽  
Francis Omujal
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Treatment Options ◽  
Chemotherapeutic Agents ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Prostate Cancer Cells ◽  
Prunus Africana

Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

Effect of cabazitaxel on the growth of human castration-refractory prostate cancer cells in vitro compared to docetaxel and on the anti-tumor properties of the angio-inhibitor PEDF in vivo.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 205-205
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Dalia Martinez-Marin ◽  
Stephanie Filleur
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Raw264.7 Macrophages

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.

Lenalidomide enhances the anti-prostate cancer activity of docetaxel in vitro and in vivo

The Prostate ◽  
2011 ◽  
Vol 72 (8) ◽  
pp. 856-867 ◽  
Author(s):  
J.Y. Henry ◽  
L. Lu ◽  
M. Adams ◽  
B. Meyer ◽  
J.B. Bartlett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Activity

scholarly journals Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP/TAZ inhibition

2021 ◽  
Author(s):  
Sue-Hwa Lin ◽  
Yu-Chen Lee ◽  
Song-Chang Lin ◽  
Guoyu Yu ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Neutralizing Antibody ◽  
Metastatic Potential ◽  
In Vivo Studies ◽  
Hybrid Cells ◽  
Tenascin C

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that enhance PCa progression. How tumor-induced bone formation enhances PCa progression is not known. We have previously shown that PCa-induced bone originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition by tumor-secreted BMP4. Here, we show that EC-to-OSB transition leads to changes in the tumor microenvironment that increases the metastatic potential of PCa cells. We found that conditioned medium (CM) from EC-OSB hybrid cells increases the migration, invasion and survival of PC3-mm2 and C4-2B4 PCa cells. Quantitative mass spectrometry (iTRAQ) identified Tenascin C (TNC) as one of the major proteins secreted from EC-OSB hybrid cells. TNC expression in tumor-induced osteoblasts was confirmed by immunohistochemistry of MDA-PCa118b xenograft and human bone metastasis specimens. Mechanistically, BMP4 increases TNC expression in EC-OSB cells through the Smad1-Notch/Hey1 pathway. How TNC promotes PCa metastasis was next interrogated by in vitro and in vivo studies. In vitro studies showed that a TNC neutralizing antibody inhibits EC-OSB-CM-mediated PCa cell migration and survival. TNC knockdown decreased, while addition of recombinant TNC or TNC overexpression increased migration and anchorage-independent growth of PC3 or C4-2b cells. When injected orthotopically, PC3-mm2-shTNC clones decreased metastasis to bone, while C4-2b-TNC overexpressing cells increased metastasis to lymph nodes. TNC enhances PCa cell migration through α5β1 integrin-mediated YAP/TAZ inhibition. These studies elucidate that tumor-induced stromal reprogramming generates TNC that enhances PCa metastasis and suggest that TNC may be a target for PCa therapy.

scholarly journals Development of Novel Chalcone Analogs as Potential Multi-Targeted Therapies for Castration-Resistant Prostate Cancer

2021 ◽  
Author(s):  
Ola Hussein ◽  
Feras Alali ◽  
Ala‐Eddin Al Mustafa ◽  
Ashraf Khalil
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
In Vivo Studies ◽  
Treatment Modalities ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Biological Studies ◽  
In Silico Admet

Prostate cancer (PCa) is the second most frequently diagnosed malignancy, as well as a leading cause of cancer-related mortality in men globally. Despite the initial response to hormonal targeted therapy, the majority of patients ultimately progress to a lethal form of the disease, castration-resistant prostate cancer (CRPC). Therefore, the objective of this study was to discover and develop novel treatment modalities for CRPC. Chalcones are among the highly attractive scaffolds being investigated for their antitumor activities. A library of 26 chalcone analogs were designed, synthesized and evaluated as potential therapies for CRPC. The design was guided by in-silico ADMET prediction in which analogs with favorable drug-likeness properties were prioritized. The new compounds were synthesized, purified and characterized by extensive structural elucidation studies. The compounds in vitro cytotoxicity was evaluated against two androgen receptor (AR)-negative prostate cancer cell lines (PC3 and DU145). Among the tested compounds, pyridine containing analogs (13, 15 and 16) showed potent antiproliferative activities with IC50 values ranging between 4.32-6.47 µM against PC3 and DU145 cell lines. Detailed biological studies of the lead molecule 16 revealed that it can significantly induce apoptosis through upregulation of Bax and downregulation of Bcl-2. In addition, compound 16 potently inhibited colony formation and reduced cell migration of AR-negative PCa cell lines (PC3 and DU145). The molecular pathway analysis showed that the anticancer activity of compound 16 is associated with blocking of ERK1/2 and Akt activities. Furthermore, compound 16 inhibited angiogenesis in the chick chorioallantoic membrane (CAM) model as compared to control. Structure-activity relationship study revealed that the cytotoxicity could dramatically improve via changing the methoxylation pattern by more than 2-folds (IC50 << 2.5 μM). These results indicate that pyridine-based chalcones could serve as promising lead molecules for the treatment of CRPC; thus, further in vitro and in vivo studies are warranted.

Antipeptidergic Therapy of Prostate Cancer: In vitro and in vivo Studies

1995 ◽  
pp. 324-331 ◽  
Author(s):  
Cornelius Knabbe ◽  
Bernhard Wagner ◽  
Gerhard Zugmaier ◽  
Ulrich Otto ◽  
Klaus Dieter Voigt
Keyword(s):  
Prostate Cancer ◽  
In Vivo Studies
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