Dexamethasone Reduces Cell Adhesion and Migration of T47D Breast Cancer Cell Line.

BACKGROUND: Aberrant expression of cell adhesion molecules and matrix metalloproteinase (MMPs) plays a pivotal role in tumor biological processes, including progression and metastasis of cancer cells. Targeting these processes and acquiring a detailed understanding of their underlying molecular mechanism are an essential step in cancer treatment. Dexamethasone (Dex) is a type of synthetic corticosteroid hormone used as adjuvant therapy in combination with current cancer treatments such as chemotherapy in order to alleviate its side effects like acute nausea and vomiting. Recent evidences suggest that Dex may have antitumor characteristics. OBJECTIVE: Dex affects the migration and adhesion of T47D breast cancer cells as well as cell adhesion molecules, e.g. cadherin and integrin, and MMPs by regulating the expression levels of associated genes. METHODS: In this study, we evaluated the cytotoxicity of Dex on the T47D breast cancer cell line through MTT assay. Cell adhesion assay and wound healing assay were performed to determine the impact of Dex on cell adhesion and cell migration, respectively. Moreover, real-time PCR was used to measure the levels of α and ß integrin, E-cadherin, N-cadherin, MMP-2, and MMP-9. RESULTS: Dex decreased the viability of T47D cells in a time and dose-dependent manner. Cell adhesion and migration of T47D cells were reduced upon Dex treatment. The expressions of α and ß integrin, E-cadherin, Ncadherin, MMP-2, and MMP-9 were altered in response to the Dex treatment. CONCLUSION: Our findings demonstrated that Dex may play a role in the prevention of metastasis in this cell line.

Emerging Molecular Functions of MicroRNA-9: Cancer Pathology and Therapeutic Implications.

MiRNAs that are characterized by small non-coding RNAs orchestrate the expression of important genes involved in cancer cell development processes, including apoptosis, proliferation, angiogenesis, metastasis, and drug resistance at the post-transcriptional level. Dysregulation of miR-9 in various cancers has been reported. Recently, miR-9 has been considered as a key miRNA in various malignancies. However, its importance in the pathogenesis of different neoplasms is not yet well defined. Accordingly, this study was conducted in order to clarify the potential roles of miR-9 in the development of various cancers, prognosis, and treatment approaches. We have shown that a large number of miR-9 targets play fundamental roles in carcinogenesis, and that is dysregulated in various cancer cells. Our findings werefound aberrant miR-9 expression in a majority of cancers. This review article generally emphasizesthe critical roles of miR-9 in cancer cell progression. Additionally, we intended to investigate the effects of down-regulation or up-regulation of miR-9 in different types of cancers. It is hoped that a good understanding of the regulatory roles of miR-9 in various cancers ishelpful for using miR-9 in clinical settings, including prognosis, diagnosis, and miRNA-based target therapy.

Correlation Between Dexamethasone and miRNAs in the Regulation of Apoptosis, Drug-resistance, and Metastasis of Cancer Cell.

Dexamethasone (Dex) is a synthetic corticosteroid hormone derived from the steroid chemical group and is applicable in treating several pathological conditions like inflammation, autoimmune disease, and malignancies. Recent investigations on the mechanism of action of Dex and its possible interactions with other cellular regulatory networks may help explain the inconsistent effects of Dex in cancer treatment. Finetuning regulation of essential post-transcriptional regulators such as microRNA (miRNAs) has indispensable impacts on modulating fundamental cellular processes, including gene expression, cell proliferation, cell cycling, and apoptosis. Dex appears to act as a double-edged sword on cancer cell progression and metastasis through regulating miRNA networks. As a proof of concept, recent investigations have proved Dex to be effective in treatment of cancer either individually or in combination with other therapeutical compounds, while several evidences have point to the controversial effects of Dex in the promotion of cancer cell survival, drug-resistance, and metastasis. In addition, it has been proven that other non-coding RNAs (ncRNAs) can also be directly or indirectly affected by Dex. In this review, we aimed to investigate the controversial effect of Dex on the cancer-related miRNAs.

Amygdalin Decreases Adhesion and Migration of MDA-MB-231 and MCF-7 Breast Cancer Cell Lines.

BACKGROUND: Cell adhesion, as dynamic interactions between cell-cell and cell-matrix, has an essential role in cancer cell migration. Integrins as cell membrane receptors are involved in cell adhesion and signal transduction. Aberrant expression of integrins is associated with the cancer cell adhesion. OBJECTIVE: Targeting the process of cell adhesion and migration could be helpful to prevent cancer cell metastasis. Amygdalin is a cyanoglycoside compound with anti-cancer properties, while its effect on cancer cell adhesion is not completely clear. METHODS: The cytotoxic effect of amygdalin on breast cancer cell lines (MCF-7 and MDA-MB- 231) and human skin fibroblast cell line as a normal cell, was evaluated through MTT assay. The cell adhesion assay and wound healing assay were performed to determine amygdalin effects on adhesion and migration of cancer cells. Further analysis was carried out to evaluate integrin α and ß levels through real-time PCR. RESULTS: We demonstrated that amygdalin diminished the cell viability of both cell lines in a time and dose-dependent manner, while amygdalin did not have any toxicity on the human skin fibroblast cell line in the same dosages. Following amygdalin treatment, the adhesion of both studied cell lines to fibronectin and collagen I decrease, and this reduction is significantly greater in the case of binding to fibronectin compared to binding to collagen. The MDA-MB-231 cell migration was decreased greater than MCF-7 cells. The levels of α and ß integrin were differentially regulated by amygdalin in both cancer cell lines. CONCLUSION: These results suggest that depending on cancer cell lines, amygdalin affects cancer cell adhesion and migration.

Inhibition of USP14 induces ER stress-mediated autophagy without apoptosis in lung cancer cell line A549.

Non-small cell lung cancer is the most common type of lung cancer, accounting for more than 80% of this tumor. Ubiquitin-specific protease (USP) 14 is one of the 100 deubiquitinating enzymes that is overexpressed in lung cancer and has been validated as a therapeutic target. The aim of this study is to determine whether the accumulation of ubiquitinated proteins results in endoplasmic reticulum (ER) stress-mediated autophagy. To inhibit USP-14, A549 lung cancer cells were treated with USP-14 siRNA and IU1-47 (20 µM). The protein level, mRNA expression, and cell cycle analysis were evaluated using Western blot, real-time PCR, and flow cytometry, respectively. We found that treating A549 cells with USP14 inhibitors significantly reduced the proliferation rate and induced cell cycle arrest at G2/M phase. We also found that USP14 inhibitors did not induce apoptosis but actually induced autophagy through accumulation of ubiquitinated proteins/ER stress/unfolded protein response (UPR) axis. Moreover, we have for the first time demonstrated that the USP14 inhibition induces ER stress-mediated autophagy in A549 cells by activation of c-Jun N-terminal kinase 1 (JNK1). In conclusion, the current investigation represents a new mechanism by which inhibition of USP14 triggers autophagy via ER stress-mediated UPR in A549 cells.

Implications for glycosylated compounds and their anti-cancer effects.

Glycosylated compounds are major secondary metabolites of plants, which have various therapeutic effects on human diseases, by acting as anti-cancer, antioxidant, and anti-inflammatory agents. Glycosylation increases stability, bioactivity, and solubility of compounds and improves their pharmacological properties. Two well-known examples of glycosylated compounds include cardiac and flavonoid, the anti-tumor activities of which have been emphasized by several studies. However, little is known about their role in the treatment or prevention of cancer. In this review, recent studies on anti-tumor properties of cardiac and flavonoid glycosides, and their mechanisms of action, have been investigated. More specifically, this review is aimed at focusing on the multifactorial properties of cardiac and flavonoid compounds as well as their correlation with signaling pathways in the treatment of cancer.

microRNAs involved in T-cell development, selection, activation, and hemostasis.

MicroRNAs (miRNAs) characterized by small, noncoding RNAs have a fundamental role in the regulation of gene expression at the post-transcriptional level. Additionally, miRNAs have recently been identified as potential regulators of various genes involved in the pathogenesis of the autoimmune and inflammatory disease. So far, the interaction between miRNAs and T lymphocytes in the immune response as a new and significant topic has not been emphasized substantially. The role of miRNAs in different biological processes including apoptosis, immune checkpoints and the activation of immune cells is still unclear. Aberrant miRNA expression profile affects various aspects of T-cell function. Accordingly, in this literature review, we summarized the role of significant miRNAs in T-cell development processes. Consequently, we demonstrated precise mechanisms that candidate miRNAs interfere in Immune response mediated by different types of T cells. We believe that a good understanding of the interaction between miRNAs and immune response contributes to the new therapeutic strategies in relation to disease with an immunological origin.