A reliable mouse model of liver and lung metastasis by injecting esophageal cancer stem cells (CSCs) through tail-vein injection.

BACKGROUND: Esophageal Squamous Cell Carcinoma (ESCC) is a highly aggressive tumor with increased metastatic potential. Recent evidence suggests that esophageal CSCs have a crucial role in tumor initiation, progression, and resistance to conventional anti-cancer therapies. The study aimed to develop mouse model to mimic the late steps of the metastasis process using a tail-vein injection of esophageal CSCs. METHODS AND RESULTS: The sphere formation assay was used to enrich CSCs. For analysis of tumorigenicity, YM-1 adherent cells and enriched CSCs were injected subcutaneously into dorsal flank of nude mice. The expression of SLUG, E-cad, and CTHRC1 genes was examined by Real-Time qRT-PCR and immunohistochemistry (IHC) methods. To assess the metastatic potential of adherent YM-1 cells and their enriched CSCs, we injected the cells into the tail vein of nude mice. Our findings showed the up-regulation of SLUG and down-regulation of E-cad in the esophageal CSC-derived tumors (ECSCTs) compared to adherent cells-derived tumors. There was no statistically significant difference between CTHRC1 gene expressions in both groups of tumors. IHC staining confirmed the higher expression of SLUG protein in ECSCTs compared to adherent cell-derived tumors. Enriched CSCs were able to metastasize to the lungs and livers after three months, but, metastasis of adherent cells wasn't observed. CONCLUSION: Our study showed esophageal CSCs injected through the tail-vein injection can migrate and metastasize to the lung and liver after three months. The developed metastatic mouse model can be a valuable and relevant model to investigate the molecular and cellular mechanisms of metastasis and develop successful targeted therapies against ESCC. The present study is one of the few studies that investigate the metastasis of esophageal cancer stem cells (ESCC type) through injection into the tail vein of nude mice.

Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis.

BACKGROUND: Current angiogenesis inhibitors target cellular vascularization processes, including proliferation, migration, and tube formation. In this study, we investigated the impact of Urtica dioica agglutinin (UDA) on the cellular vascularization process. METHODS AND RESULTS: Various concentrations of UDA were applied to normal (HUVEC, MCF-10 A, and HDF from humans, and L-929 from mice) and cancer (A431 and U87 from humans, and 4T1 from mice) cell lines at different times. The MTT, cell migration assay, differentiation of endothelial cells, expression of VEGF-A/VEGF-R2, and integrin α2 were evaluated. The MTT results demonstrated that UDA was non-toxic to normal cells while inhibiting the growth of neoplastic cells. The migratory capacity of HUVECs and U87 glioblastoma cells was inhibited by UDA in the wound repair model. This lectin inhibited HUVEC-induced vessel sprouting in the collagen-cytodex matrix. In addition, UDA treatment reduced VEGF-integrin cross-talk in HUVECs, confirming the anti-angiogenic activity of this molecule. CONCLUSIONS: Based on our findings, UDA may have an effect on cancer cell proliferation and vascularization events while causing minimal toxicity to normal cells via binding glyco-conjugates containing GlcNAc/man oligomers like EGFR. This is a blue clue for the angiogenesis-related therapeutic importance of UDA.

Synergistic effects of BAY606583 on docetaxel in esophageal cancer through modulation of ERK1/2.

Docetaxel (DTX) is a taxane chemotherapy agent used to treat many types of cancers, including esophageal squamous cell carcinoma. Adenosine is a purinergic signaling molecule that contributes to cancer cell proliferation via A2B adenosine receptor (A2BAR) activation. Extracellular signal-regulated protein kinase (ERK) plays a crucial role in cell proliferation in various types of cancers. Stimulation of A2BAR involves a regulated ERK signaling pathway, and might provide a fascinating approach for treatment, leading to decreased proliferation in certain tumors that express A2BAR. Recent studies demonstrated that DTX and A2BAR have anticancer effects. The current study was designed to investigate the synergistic effect of the A2BAR agonist (BAY606583) on DTX in inducing antiproliferation effects on esophageal squamous cells carcinoma (ESCCs). The cell viability was assessed using the MTT assay in KYSE-30 and Ym-1 cells. In addition, the synergistic effect of DTX on the A2BAR agonist was evaluated. Subsequently, apoptosis was assessed by Annexin-V and propidium iodide staining, and Bcl-2, Bax, and ERK1/2 protein-level expressions were evaluated by Western blot. Use of BAY606583 and cotreatment of DTX and BAY606583 significantly decreased cell proliferation in KYSE-30 and Ym-1 cell lines. The use of BAY606583 and cotreatment of DTX with the A2BAR agonist induced apoptosis in KYSE-30 and Ym-1 cells. Western blot analysis revealed that the use of the A2BAR agonist and cotreatment of DTX with the A2BAR agonist inhibited the expression of apoptotic regulatory proteins as well as the expression of ERK1/2 proteins. Our findings suggested that use of BAY606583 and cotreatment of BAY606583/DTX have an antiproliferative effect on ESCC cell lines through ERK signaling pathway inhibition. BAY606583 has a synergistic effect on DTX, which could be used as an adjuvant for esophageal cancer therapy.

Melatonin: A smart molecule in the DNA repair system.

DNA repair is an important pathway for the protection of DNA molecules from destruction. DNA damage can be produced by oxidative reactive nitrogen or oxygen species, irritation, alkylating agents, depurination and depyrimidination; in this regard, DNA repair pathways can neutralize the negative effects of these factors. Melatonin is a hormone secreted from the pineal gland with an antioxidant effect by binding to oxidative factors. In addition, the effect of melatonin on DNA repair pathways has been proven by the literature. DNA repair is carried out by several mechanisms, of which homologous recombination repair (HRR) and non-homologous end-joining (NHEJ) are of great importance. Because of the importance of DNA repair in DNA integrity and the anticancer effect of this pathway, we presented the effect of melatonin on DNA repair factors regarding previous studies conducted in this area.

Antioxidant supplementations ameliorate PCOS complications: a review of RCTs and insights into the underlying mechanisms.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use.

Upregulation of Fucosyltransferase 3, 8 and protein O-Fucosyltransferase 1, 2 genes in esophageal cancer stem-like cells (CSLCs).

Recently, studies have shown that Fucosylation plays an important role in the invasion and metastatic process of CSLCs. Understanding the expression pattern of fucosyltransferase (FUT) genes may help to suggest better-targeted therapy strategies for esophageal squamous cell carcinoma (ESCC). The study aimed to address the expression pattern of FUT gene variants in esophageal CSLCs and parental adherent cells. Sphere formation method was used to enrich CSLCs. Expression of FUT genes was examined in tumor sphere and parental adherent cells using the RT-PCR method and then relative expression of detected variants was performed by the Real-Time PCR method in both groups. The detected FUTs, also, were assessed in fresh ESCC tumors and the matched healthy controls. Analysis of The cell surface carbohydrate Lewis x (LeX, CD15) was performed by flow cytometry. Molecular analysis showed that the expression of FUT 3, 8 and POFUT1, 2 genes in tumorsphere were significantly higher than parental adherent cells. Analysis of fresh ESCC tumor tissues and the matched healthy controls showed that FUT8 and POFUT1, 2 genes in contrast to FUT 3 have higher expression in tumor tissues than controls. Flow cytometric analyses revealed that tumorsphere and their parent cells do not differ significantly in Lewis x surface marker. The present study showed that FUT 3, 8 and POFUT1, 2 genes upregulated in esophageal CSLCs in comparison to adherent cells. Understanding the expression pattern of FUT gene variants may help to suggest better-targeted therapy strategies for ESCC.

The role of substance P/neurokinin 1 receptor in the pathogenesis of esophageal squamous cell carcinoma through constitutively active PI3K/Akt/NF-κB signal transduction pathways.

One of the most prevalent malignancies is esophageal squamous cell carcinoma (ESCC), which is associated with high morbidity and mortality. Substance P (SP), as one of the peptides released from sensory nerves, causes the enhancement of cellular excitability through the activation of the neurokinin-1 (NK1) receptor in several human tumor cells. Aprepitant, a specific, potent, and long-acting NK1 receptor antagonist, is considered as a novel agent to inhibit proliferation and induce apoptosis in malignant cells. Since the antitumor mechanism of aprepitant in ESCC is not completely understood, we conducted this study and found that aprepitant induced growth inhibition of KYSE-30 cells and arrested cells in the G2/M phase of the cell cycle. Aprepitant also caused apoptotic cell death and inhibited activation of the PI3K/Akt axis and its downstream effectors, including NF-κB in KYSE-30 cells. Besides, quantitative real-time (qRT)-PCR analysis showed a significant down-regulation of NF-κB target genes in KYSE-30 cells, indicating a probable NF-κB-dependent mechanism involved in aprepitant cytotoxicity. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising therapeutic strategy against ESCC.

Increased expression of miR-146a, miR-10b, and miR-21 in cancer stem-like gastro-spheres.

BACKGROUND: Gastric cancer remains one of the leading causes of cancer-associated mortalities globally. Accumulating evidence support the presence of gastric cancer stem cells (CSCs) and their role in the pathogenesis and therapeutic challenges of gastric cancer. MicroRNAs (miRNAs) may be influenced by the cellular differentiative state and as critical regulators of the cellular fate in development and cancer, can modulate the behavior of CSCs too. Here, we aimed to investigate the expression relevance of three prognostic miRNAs (miR-21, miR-10b, and miR-146a) in CSCs of AGS and MKN-45 gastric cancer cell lines. METHODS: Serial sphere-forming assay in serum-free culture medium was used to enrich the cellular population with stem-like properties. Gastro-spheres were characterized by evaluating the stemness gene expression, clonogenicity, and resistance to docetaxel and cisplatin in comparison with their parental cells. The expression level of miRNAs in gastro-spheres and their parental cells was measured using quantitative reverse transcription polymerase chain reaction. RESULTS: Gastro-spheres from both cell lines exhibit stem-like properties: upregulated stemness associated genes (P < 0.05), more colonogenicity and more resistance to docetaxel (P < 0.05). MKN-45 gastro-spheres exhibited upregulated expression of miR-21 (1.8-folds), miR-10b (1.34-folds) and miR-146a (4.8-folds; P < 0.05) compared with the parental cells. AGS-derived gastro-spheres showed upregulation of miR-21 (4.7-folds; P < 0.01), miR-10b (15.2-folds; P < 0.001) and miR-146a (39.3-folds; P < 0.05). CONCLUSION: Our data exhibited upregulation of miR-21, miR-10b, and miR-146a in the stem-like gastro-spheres; however; their function in gastric CSCs remains to be verified by further experiments.

Fucosyltransferase 3 and 8 promote the metastatic capacity of cancer stem-like cells via CD15s and E-cadherin in esophageal cancer.

Objectives: Esophageal cancer stem cells (ECSCs) have been identified as the subset of cells within esophageal squamous cell carcinoma that possess tumorigenic, invasive, and metastatic properties. One important aspect of cancer metastasis is the binding of sialyl-Lewis X (CD15s) with E- or P-selectin, which facilitates the adhesion and migration of cancer cells to distant sites. This study was conducted to investigate the impact of fucosylation processes on the metastatic behavior of ECSCs. Materials and Methods: The esophageal cancer cell line (KYSE-30) was cultured and divided into control and 2F-peracetyl fucose (2F-PerAcFuc) treated groups. Spheres were harvested from these cultures. Cell invasion assay and qPCR were conducted to examine migration and marker expression in both groups. Cancer cell line-derived xenografts were established in nude mice to validate findings in vivo. Results: Our results initially indicated that the addition of 2F-PerAcFuc, an inhibitor of fucosylation, resulted in the down-regulation of the Fut3/CD15s pathway in both cancer stem-like cells and the xenograft model. Measurements of subcutaneous xenograft tumor volume revealed a significant decrease in tumor size among nude mice after treatment with 2F-PerAcFuc. Additionally, a reduction in Fut8/E-cadherin levels was observed in the xenograft model of nude mice. Furthermore, the administration of 2F-PerAcFuc lowered the levels of fucosylated glycoconjugates in nude mice. Conclusion: Our data suggest that inhibition of fucosyltransferase 3 and 8 can reduce the metastatic capacity of cancer stem-like cells by down-regulating CD15s and E-cadherin in a mouse model of esophageal cancer.

Lower serum zinc level is associated with higher fasting insulin in type 2 diabetes mellitus (T2DM) and relates with disturbed glucagon suppression response in male patients.

AIMS: Zinc ion can play critical role in glycemic control in diabetes mellitus (DM), contributing to both insulin synthesis and secretion. In this study, we aimed to investigate the level of zinc in diabetic patients and its association with glycemic parameters, insulin, and glucagon level. METHODS: 112 individuals (59 cases of type 2DM and 53 non-diabetic controls) were included in this study. Biochemical parameters (FBG, 2hpp, HbA1C), and zinc level in the serum were measured using colorimetric assays. Insulin and glucagon were measured by ELISA method. HOMA-IR, HOMA-B, reciprocal HOMA-B, and Quicki indices were calculated using appropriate formula. For further analysis, patients were divided into two groups: high (>135.5 µg/dl) and low (<135.5 µg/dl) zinc. Glucagon suppression was considered yes if 2hpp glucagon < fasting glucagon. RESULTS: Our results showed that serum Zn level in type 2 DM patients was lower than control (P value=0.02). Patients with lower Zn had higher fasting insulin (P value=0.006) and higher ß-cell activity index (HOMA-B, p value=0.02), however fasting glucagon and parameters of hyperglycemia (FBG, 2hpp, Hba1C) were not different. Moreover, insulin sensitivity and resistance indices (Quicki, HOMA-IR,1/HOMA-IR) showed non-significantly improved status in high Zn group. We found non-significant association between glucagon suppression and Zn level in both genders (N = 39, p value = 0.07), however, it was significant in males (N = 14, p value = 0.02). CONCLUSION: Altogether, our results indicated reduced serum Zn in type 2DM can exacerbate hyperinsulinemia and glucagon suppression (only significant in the male), highlighting its importance in type 2DM control.

Anti-cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation.

BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer-related death, despite many advances in treatment, the survival of patients still remains poor. In recent years, the N6-methyladenosine (m6A) has been introduced as one of the most important modifications at the epitranscriptome level, with an important role in the mRNA regulation in various diseases, such as cancers. The m6A is regulated by different factors, including FTO as a demethylase. The m6A modification, especially through FTO overexpression has an oncogenic role in different cancer types such as EC. Recent studies showed that entacapone, a catechol-o-methyl transferase (COMT) inhibitor currently applied for Parkinson's disease, can inhibit FTO enzyme. AIMS: In this study, we aimed to investigate the effect of entacapone as an FTO inhibitor on the m6A level and also apoptosis and cell cycle response in KYSE-30 and YM-1 of esophageal squamous cancer cell (ESCC) lines. METHODS: Cell toxicity and IC50 of entacapone were evaluated using The MTT assay in YM-1 and KYSE-30 cells. Cells were treated into two groups: DMSO (control) and entacapone (mean IC50 ). Total RNA was extracted, and m6A levels were measured via the ELISA method. Subsequently, the apoptosis and cell cycle dys-regulation were detected by annexin-V-FITC/PI staining and PI staining via flow cytometry. RESULTS: Entacapone has the cytotoxicity effect on both esophageal cancer cell lines compared to normal PBMC cells. As well, entacapone treatment (140 µM) can induce apoptosis (KYSE-30: 50%. YM-1:22.6%) and has a modulatory effect on cell cycle progression in both YM-1 and KYSE-30 cells (p-value<.05). However, no significant difference in the m6A concentration was observed. CONCLUSION: Our findings suggested that entacapone has the inhibitory effect on ESCC cell lines through induction of the apoptosis and modulation of the cell cycle without toxicity on the normal PBMC.

Gene expression pattern of adenosine receptors in lung tumors.

BACKGROUND: Adenosine, a purine nucleoside, plays an important function in the pathogenesis of cancer through interaction with the cell surface G protein-coupled adenosine receptors. It is important to determine the expression pattern of these receptors in different cancers. Previously in our lab, we found up-regulation of A1 adenosine receptor (AR) in lung tumors playing as a putative target for cancer cell inhibition, and here we aimed to investigate the significance of other adenosine receptor isoforms (A2aAR, A2bAR, and A3AR). METHODS: In this study, first of all, we evaluated the adenosine receptors gene expression in the bioinformatics database (GENT2). Then the genes expression was measured experimentally in the 20 lung cancer tumor tissues in comparison to the matched tumor-adjacent normal tissue (as control). The mRNA expression of receptors was evaluated by real-time PCR. The tumors were categorized by the tumor size and the gene expression change was evaluated. RESULTS: The experimental results indicated a significant increase in A2aAR (p value = .021) and A3AR (p value = .01) expression in lung tumor tissues compared to the adjacent tumor margins which were in accordant to bioinformatics analysis. We found a non-significant increase in A2bAR expression; however, when comparing the patients according to the tumor size, our data showed that the expression of A2bAR adenosine receptor in patients with smaller lung tumor sizes was higher than the other group (p = .011). CONCLUSION: The results of this study showed that adenosine receptors A3AR, and A2aAR are highly expressed in lung tumors relative to tumor-adjacent normal tissue. We suggest that overexpression of adenosine receptors in lung cancer is due to their regulatory role in various aspects of lung cancer.

A1 adenosine receptor antagonist induces cell apoptosis in KYSE-30 and YM-1 esophageal cancer cell lines.

Background and aim: Adenosine A1 receptor (AA1R) has been shown to have an inhibitory effect on cell growth in several cancers; however, its function in esophageal cancer is still unclear. In this study, we examined the effect of AA1R on cell growth and apoptosis in esophageal cancer cells. Materials and methods: In this study, YM-1 and KYSE-30 esophageal cancer cell lines were cultured. AA1R gene expression was determined by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). As well, the AA1R antagonist (DPCPX) effect on cell viability was evaluated by the MTT assay. Moreover, apoptosis was assessed by annexin-V and propidium iodide staining, and the caspase-3/7 activity assay kit. Result: qRT-PCR results indicated that the AA1R was expressed in YM-1 and KYSE-30 cells. In addition, DPCPX significantly decreased cell proliferation in both cell lines. Furthermore, the A1AR antagonist induced apoptosis in KYSE-30 and YM-1 cells. After treatment of both cell lines with DPCPX, the caspase 3/7 activity was increased. Conclusion: Our finding indicates the AA1R antagonist induces apoptosis through caspase 3/7 activation and can be considered a potential target in esophageal cancer therapy.

Effects of Urtica dioica agglutinin on glycotargeting of the vasculature: an in ovo study on chicken embryo.

The angiogenesis process is a pivotal cellular process involved in both developmental and pathological circumstances. In this study we investigated effect of Urtica dioica agglutinin (UDA), as an unusual phyto-lectin from the chitin-binding protein family, on the angiogenesis of chicken embryos. The UDA was extracted from plant rhizomes and purified by affinity chromatography column. The activity of this lectin was assayed by hemagglutination test on the human RBCs. Anti-angiogenic effect of UDA on the extra-embryonic layer of the chick egg was studied in the different concentrations. Our results showed that the minimum concentration of UDA for agglutination were 48.00 and 15.00 µg mL-1 in macro- and microscopic studies, respectively. Because the number and length of the vessels were dramatically decreased at 100 µg kg-1 of UDA, the lectin had an inhibitory effect on angiogenesis of the embryonic vasculature of the chick. We concluded that UDA might target the vascularization events through binding to GlcNAc-conjugates. More investigations are needed to clarify the angiogenesis-related therapeutic roles of this interesting biomolecule.

The Role of Micro RNAs in Regulating PI3K/AKT Signaling Pathways in Glioblastoma.

Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been introduced as a novel target for treating glioblastoma via regulation of apoptotic signaling pathway, remarkably PI3K/AKT, which affect cellular functions and blockage or progression of the tumor. In this review, we focus on PI3K/AKT signaling pathway and other related apoptotic processes contributing to glioblastoma and investigate the role of micro RNAs interfering in apoptosis, invasion and proliferation of glioma through such apoptotic processes pathways. Databases NCBI, PubMed, and Web of Science were searched for published English articles using keywords such as 'miRNA OR microRNA', 'Glioblastoma', 'apoptotic pathways', 'PI3K and AKT', 'Caspase signaling Pathway' and 'Notch pathway'. Most articles were published from 7 May 2015 to 16 June 2020. This study focused on PI3K/AKT signaling pathway affecting glioma cells in separated subparts. Also, other related apoptotic pathways as the Caspase cycle and Notch have been also investigated. Nearly 40 miRNAs were found as tumor suppressors or onco-miRNA, and their targets, which regulated subcomponents participating in proliferation, invasion, and apoptosis of the tumoral cells. Our review reveals that miRNAs affect key molecules in signaling apoptotic pathways, partly PI3K/AKT, making them potential therapeutic targets to overcome the tumor. However, their utility as a novel treatment for glioblastoma requires further examination and investigation.

Decreased Expression of LAMB3 Is Associated with Esophageal Cancer Stem Cell Formation.

Purpose: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer. The main cause of death in ESCC is related to relapse, metastasis, and resistance to cancer therapy. Recent studies have shown that a minor subset of cancer cells, known as cancer stem cells (CSCs), are responsible for tumor formation initiation and cancer progression. Understanding the genes associated with CSCs and metastasis can help in targeted cancer therapy. The aim of this study was to assess the expression of LAMB3 and TOP2A metastasis-associated genes in CSCs and adherent cells in the xenograft mouse model. Methods: Esophageal CSCs were enriched by the sphere formation method. The expression level of LAMB3 and TOP2A genes were evaluated in spheres and adherent cells in vitro by qRT-PCR. A xenograft mouse model was established to investigate the tumorigenesis and metastasis potential by subcutaneous and tail vein injection of CSCs and adherent YM-1 cells. Consequently, LAMB3 and TOP2A expression at the mRNA level was assessed in tumors. Immunohistochemistry was also used to evaluate the LAMB3 expression at the protein level in tumors. Results: CSCs-derived tumor was developed more quickly than the adherent cells-derived tumor. LAMB3 at mRNA and protein level was significantly down-regulated in sphere-derived tumor compared with adherent cells-derived tumor (P value <0.05). TOP2A expression was almost similar in both sphere cells and adherent cells and there was no significant difference. Conclusion: we concluded that YM-1 spheres have CSCs characteristics in vitro with high capability of tumorigenicity in vivo. Our results were also shown that the LAMB3 expression was decreased in YM-1 spheres suggesting LAMB3 association with sphere formation.

SOX2OT lncRNA Inhibition Suppresses the Stemness Characteristics of Esophageal Tumorspheres.

BACKGROUND: SOX2OT is a novel cancer associated long non-coding RNA (LncRNA) with higher expression in variable tumor tissues, including esophageal squamous cell carcinoma (ESCC). It also plays an important function in embryonic neuronal development. Regarding its function in both stemness and carcinogenesis, here, we aimed to investigate its expression and function in tumorspheres of the esophagus using the RNAi method. MATERIAL & METHODS: Two esophageal squamous cancer cells (ESCC): KYSE30 and YM1 cells were used for sphere enrichment. Cells were transfected with SOX2OT targeting and control siRNA. The size and the number of spheres were measured using light microscopy. Gene expression of the pluripotency genes was measured by qRT-PCR and docetaxel chemoresistance was assessed by MTS viability assay. RESULTS: Our findings showed that ESCC tumorspheres overexpress SOX2OT gene along with other stemness genes (SOX2, OCT4A, and Nanog) compared to their original cancer cells. RNAi experiments indicated that SOX2OT knockdown can suppress the stemness-related gene expression, sphere formation ability (both size and number), and docetaxel resistance as three of the main cancer stem cell characteristics of tumorspheres. CONCLUSION: Altogether our results showed the regulatory role of SOX2OT in pluripotency and stemness in ESCC tumorspheres. Our results suggest a potential application of SOX2OT inhibition in combination with docetaxel for ESCC inhibition in vitro.

The Use of Bio-Active Compounds of Citrus Fruits as Chemopreventive Agents and Inhibitor of Cancer Cells Viability.

Common therapy of cancer, such as chemotherapy, has various side effects for the patients. In recent studies, new therapeutic approaches in cancer treatment are adjuvant therapy, along with a reduction in side effects of chemotherapy drugs. Treatment by herbal medicines may have some advantages over treatment with single purified chemicals, also in terms of side effects, the use of plants in cancer treatment is a more secure method. Citrus fruits are one of the most consumed natural products in the world due to the presence of various metabolites and bioactive compounds, such as phenols, flavonoids and, carotenoids. Bioactive compounds of citrus modulate signaling pathways and interact with signaling molecules such as apoptotic and cell cycle (P53, P21, etc.) and thus have a wide range of pharmacological activities, including anti-inflammatory, anti-cancer and oxidative stress. The findings discussed in this review strongly support their potential as anti-cancer agents. Therefore, the purpose of this review was to examine the effects of active compounds in citrus as a therapy agent in cancer treatment.

Knockdown of TAZ decrease the cancer stem properties of ESCC cell line YM-1 by modulation of Nanog, OCT-4 and SOX2.

Cancer stem cells are a rare population in tumors with high metastatic potential and resistance to treatment. Recent strategies in cancer treatment have focused on targeting important signaling pathways that have an important role in maintaining CSC populations. TAZ (transcriptional co-activator with PDZ-binding motif) is a key downstream of the Hippo pathway which plays a fundamental role in the survival of CSCs from different origins, however, no data on the role of TAZ in esophageal cancer are available. Our findings showed that esophageal CSCs enriched from the YM-1 cell line have stemness properties. We found that TAZ was strongly expressed in esophageal CSCs and knockdown of TAZ in esophageal CSCs results in reduced colony formation and cell migration. Moreover, this data indicated that TAZ knockdown reduces the expression of SOX-2, OCT-4, and Nanong in esophageal CSCs. Taken together, the results of the current study suggested that TAZ has a crucial role in the biology of esophageal CSCs.