Prostate Cancer Growth Inhibition by 1-(3,5-Dimethylphenyl)–6-methyl-1H-pyrazolo[4,3-c]pyridin-4(5H)-one via Down-regulation of Phosphorylation PI3K/AKT and STA3/JAK2

Xue, Jingxin; Zhang, Zhenwei; Hu, Heyi

doi:10.1134/s160767292006006x

Cited by 4 publications

(1 citation statement)

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“…A previous study by Kharaziha et al reported that 22Rv1 cells exhibit constitutive activation of ERK1/2 and that its inhibition with the multi-tyrosine kinase inhibitor sorafenib induced cell death via activation of the pro-apoptotic protein Bad [ 54 ]. Likewise, the prooxidant agent 1-(3,5-dimethylphenyl)-6-methyl-1H-pyrazolo[4,3-c]pyridin-4 (5H)-one (DPMPP) exerted a cytotoxic effect in 22Rv1 cells by causing cell cycle arrest in S phase and apoptosis accompanied with an increase in the reactive oxygen species production and with an inhibition of the PI3K/AKT/ERK phosphorylation [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells

et al. 2021

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A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Because of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

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Section: Resultsmentioning

confidence: 99%