RESUMO
BACKGROUND: Breast cancer is one of the most common diseases worldwide that affects women of reproductive age. miR-221 and miR-222 are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/ß-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulating miR-221 and miR-222 expression through Wnt/ß-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. METHOD: Chitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression of miR-221 and miR-222 and Wnt/ß-catenin pathway genes was measured. RESULTS: The level of miR-221 and miR-222 and ß-catenin genes decreased in MCF-7 and MDA-MB-231 cells and WIF1 gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs and WIF1 gene expressions were increased following CC-CUR administration and ß-catenin decreased by administration of CUR. CONCLUSION: Although the composite form of curcumin decreased the expression of miR-221 and miR-222 in MCF-7 and MDA cells, with significant decreasing of ß-catenin and increasing of WIF1 gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/ß-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.
Assuntos
Neoplasias da Mama , Quitosana , Curcumina , MicroRNAs , Feminino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Quitosana/farmacologia , Curcumina/farmacologia , Células MCF-7 , MicroRNAs/metabolismo , Via de Sinalização Wnt/genética , NanopartículasRESUMO
Hedgehog (Hh) is a conserved signaling pathway that is involved in embryo development as well as adult tissue maintenance and repair in invertebrates and vertebrates. Abnormal activation of this pathway in various types of malignant drug- and apoptosis-resistant tumors has made it a therapeutic target against tumorigenesis. Thus, understanding the molecular mechanisms that promote the activation or inhibition of this pathway is critical. Long non-coding RNAs (lncRNAs), a subclass of non-coding RNAs with a length of > 200 nt, affect the expression of Hh signaling components via a variety of transcriptional and post-transcriptional processes. This review focuses on the crosstalk between lncRNAs and the Hh pathway in carcinogenesis, outlines the broad role of Hh-related lncRNAs in tumor progression, and illustrates their clinical diagnostic, prognostic, and therapeutic potential in tumors.
Assuntos
Neoplasias , RNA Longo não Codificante , Adulto , Animais , Carcinogênese/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias/tratamento farmacológico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: Gliomas are the most prevalent type of malignant primary brain tumors. Despite the availability of several treatment modalities, these tumors have poor prognostic features. Aberrant Hedgehog (Hh) signaling has been found to be implicated in the development of numerous malignancies including gliomas. Naringenin appears to have anti-proliferative and anti-cancer properties. However, there is no report describing its effects via the Hh signaling pathway on the C6 glioblastoma cell line. The current study was set to examine the anti-cancer effects of naringenin on C6 cells in order to determine the effect of this compound on the Hh signaling pathway. METHODS: The anti-proliferative and apoptotic effects of naringenin against C6 and 3T3 fibroblast cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin-V/PI dual staining assay, respectively. The effect of naringenin on the migration of C6 cells was evaluated by the migration scratch assay. To assess the anti-cancer effect of naringenin on the Hh signaling pathway, the expression of Gli-1, Smo, and Sufu at protein levels in C6 cells was analyzed using western blotting. RESULTS: The obtained data indicated that naringenin exerted higher cytotoxicity against C6 cells (IC50 value of 114 ± 3.4 µg/mL) than normal 3T3 fibroblasts (IC50 value of 290 ± 7 µg/mL). Naringenin (114 µg/mL) also induced stronger apoptotic effects on C6 cells than 3T3 cells after 24 h of incubation. Furthermore, naringenin at a concentration of 114 µg/mL and a lower concentration of 60 µg/mL inhibited the migration of the C6 cell line. In addition, naringenin at a concentration of 114 µg/mL significantly decreased the expression of Gli-1 and Smo and elevated the expression of Sufu at the protein level in the C6 cell line. CONCLUSION: These data represent that naringenin may have a potential effect on the management of the proliferation and metastasis of malignant gliomas by inhibiting the Hh signaling pathway.
