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<p>Prostate cancer is leading to cancer‐related mortality in numerous men each yearworldwide. While there are several treatment options, acquired drug resistance mostlylimits the success of treatments. Therefore, there is a need for the development ofinnovative treatments. Curcumin is one of the bioactive polyphenolic ingredientsidentified in turmeric and has numerous biological activities, such as anti‐inflammatoryand anticancer. In the present study, we investigated the effect of curcumin on the ER‐associated degradation (ERAD) and estrogenic signaling in prostate cancer cells. Theantiproliferative effect of curcumin on human androgen‐dependent prostate cancer celllines LNCaP and VCaP was estimated by WST‐1 assay. Morphological alterations wereinvestigated with an inverted microscope. We investigated the effect of curcumin onERAD and estrogen signaling proteins by immunoblotting assay. To evaluate the impact ofcurcumin on endoplasmic reticulum (ER) protein quality‐related, the expression level of 32genes was analyzed by quantitative reverse transcription polymerase chain reaction. Thenuclear translocation of estrogen receptor was examined by nuclear fractionation andimmunofluorescence microscopy. We found that curcumin effectively reduced theproliferation rates of LNCaP and VCaP cells. ERAD proteins; Hrd1, gp78, p97/VCP, Ufd1and Npl4 were strongly induced by curcumin. Also, the steady‐state level of polyubiquitinwas increased in a dose‐dependent manner in both cell lines. Curcumin administrationremarkably decreased the protein levels of estrogen receptor‐alfa (Erα), whereas estrogenreceptor‐beta unaffected. Additionally, curcumin strongly restricted the nucleartranslocation of Erα. Present data suggest that curcumin may be effectively used intherapeutic approaches associated with the targeting ER protein quality controlmechanism and modulation of estrogen signaling in prostate cancer.<br></p> |
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