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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.

Background: Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer in high-risk areas in the world, we have investigated the effect of high doses of selenium on gene expression in the esophagus of rats treated with N-nitrosomethylbenzylamine (NMBA). Materials and methods: Esophageal squamous cell carcinoma (ESCC) was induced in Sprague Dawley male rats with NMBA (0.5 mg/kg BW, s.c, three times per week for 5 weeks). Rats in the treated groups were given 0.3, 1.5, and 3 mg/kg body weight sodium selenite for 20 weeks. After euthanizing the rats, esophageal tissue and blood was collected to assess the effects of high dose selenium. Pathological analysis was performed to diagnose preneoplastic lesion in the rat esophagus. Serum malondialdehyde and whole blood glutathione peroxidase activity was measured. Furthermore, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-β, and MGMT were analyzed and compared between groups. Results: In the esophagus of rats treated with NMBA, increasing selenium levels significantly increased the mRNA levels of cyclin D1 and NF-κB p65.The concentrations of cyclin D1 was also significantly increased by high-dose selenium. Moreover, excess dietary selenium had no significant effect on serum MDA but significantly increased GPx activity. Conclusion: The present study proved that high dose of inorganic selenium increases the mRNA levels of cyclin D1 and NF-κB p65 in the esophagus of rats treated with NMBA and may promote carcinogenesis by enhancing oxidative stress, inflammation, and cell proliferation.

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.

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.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.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 ICEntacapone 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.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.

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).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.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).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.

Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer, we have investigated the effect of high doses of selenium on gene expression in the normal esophageal tissue of rats. Twenty male rats were randomly divided into four groups: control group, group 2 mg Se/L, 10 mg Se/L, and 20 mg Se/L rats fed with a basal basic diet and 2, 10, and 20 mg Se/L as sodium selenite in drinking water, respectively, for 20 weeks. Serum malondialdehyde and glutathione peroxidase activity were measured. Moreover, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-β, and MGMT in the esophageal tissue were analyzed and compared between the four groups. In normal esophageal tissue, selenium supplementations (2, 10, and 20 mg Se/L) increased the mRNA levels of cyclin D1, P53, KRAS, NF-κB p65, and MGMT and decreased the mRNA level of TGFß1. The concentrations of cyclin D1 and MGMT were also significantly increased by selenium supplementations. Selenium supplementations had no significant effect on serum MDA but significantly increased GPX activity. The present study suggests that selenium supplementation (2, 10, and 20 mg Se/L) affects gene expression related to inflammation, Cell proliferation, and apoptosis in the normal esophageal tissue. However, there were no observed abnormalities other than reduced growth with supplementation of 20 mg/L as Na2SeO3 in rats.

MicroRNAs (miRNAs) play a vital role in various cell biology processes, including cancer formation. These small non-coding RNAs could function as diagnostic and prognostic markers. They may involve esophageal squamous cell carcinoma (ESCC) and distinctive miRNA expression profiles; they are also known as therapeutic targets in human diseases. Therefore, in this study, the function of miRNAs was reviewed regarding the prognosis and diagnosis of ESCC. The changes in miRNAs before and after cancer therapy and the effects of miRNAs on chemo-susceptibility patterns were also investigated. MiRNA delivery systems in ESCC were also highlighted, providing a perspective on how these systems can improve miRNA efficiency.

Natural products are considered recently as one of the source for production of efficient therapeutical agents for breast cancer treatment. In this study, a sesquiterpene lactone, 13-O-acetylsolstitialin A (13ASA), isolated from Centaurea cyanus, showed cytotoxic activities against MCF-7 and MDA-MB-231 breast cancer cell lines using standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To find the mechanism of action of cytotoxicity, annexin V/propidium iodide (PI) staining was performed for evaluation of apoptosis. This process was further confirmed by immunoblotting of anti- and proapoptotic, Bcl-2 and Bax, proteins. Cell cycle arrest was evaluated by measurement of fluorescence intensity of PI dye and further confirmed by immunoblotting of Cdk-4 and cyclin D1. Mitochondrial transmembrane potential (ΔΨm) and generation of reactive oxygen species (ROS) were measured using the JC-1 and DCFDA fluorescence probes, respectively. These experiments showed that 13ASA is a potent cytotoxic agent, which activates apoptosis-mediated cell death. In response to this compound, Bax/Bcl-2 ratio was noticeably increased in MCF-7 and MDA-MB-231 cells. Moreover, 13ASA induced cell cycle arrest at subG1 and G1 phases by decreasing protein levels of cyclin D1 and Cdk-4. It was done possibly through the decrease of ΔΨm and increase of ROS levels which induce apoptosis. In conclusion, this study mentioned that 13ASA inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cell lines through the induction of cell cycle arrest, which triggers apoptotic pathways. 13ASA can be considered as a susceptible compound for further investigation in breast cancer study.

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

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.

Euphorbia kopetdaghi grows wild in the Northeast parts of Iran. Phytochemical study of its aerial parts led to the isolation of two undescribed cyclomyrsinol macrocyclic diterpenes with a new tetrahydrofuran oxidation pattern containing a hemiacetal group named: kopetdaghinane A and B. The structure of the isolated compounds was elucidated by extensive spectroscopic methods. Cytotoxic activity of kopetdaghinane A was evaluated using standard MTT assay against MCF-7 breast cancer and OVCAR-3 ovary cells. HUVEC cells were used as a normal cell line for calculation of the selectivity index. The MTT showed cyclomyrsinol diterpene has a significant cytotoxic effect with good selectivity indexes against both cell lines but with more selectivity against MCF-7 cells. Apoptosis induction by cyclomyrsinol treatment was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to kopetdaghinane A treatment, while the expression of Bax protein was increased. Moreover, the apoptotic effect of cyclomyrsinol was shown to be related to ROS production, and loss of mitochondrial membrane potential (ΔΨm). Taken together, these results showed that kopetdaghinane A inhibits the growth of MCF-7 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may be considered as an investigational compound in breast cancer preclinical study.

Local chemotherapy with biocompatible drug-delivery systems prolongs survival in patients. Due to the biocompatibility and high loading capacity, bentonite nanoclay is a good candidate for the fabrication of drug-delivery vehicles. In this study, doxorubicin-bentonite nanoclay complex (DOX-Bent complex) was prepared for the first time as a sustained-release drug-delivery system for intratumoural chemotherapy of melanoma. An efficient loading of DOX on 1 mg of bentonite nanoclay as high as 994.45 ± 4.9 µg was obtained at a 30:1 DOX:bentonite nanoclay mass ratio. The DOX-Bent complex showed a low initial burst release of DOX in the first 24 h of release, followed by a sustained-release pattern for 21 days. The cumulativein vitrorelease of DOX from the DOX-Bent complex at pHs 6.5 and 7.4 revealed that the DOX-Bent complex can distinguish between tumour and normal tissues and express specific drug release at the tumour site. The results of cytotoxicity experiments indicated that the release pattern of DOX can supply sufficient DOX to inhibit growth of the melanoma cancer cell with an IC50 of 0.29 ± 0.07 µg/mL. It is thus suggested that the DOX-Bent complex be introduced as a drug-delivery system for effective local cancer therapy.

It has been reported that cancer stem cells (CSCs) may play a crucial role in the development, recurrence and metastasis of breast cancer. Targeting signaling pathways in CSCs is considered to be a promising strategy for the treatment of cancer. Here, we investigated the role of the A2B adenosine receptor (A2BAR) and its associated signaling pathways in governing the proliferation and viability of breast cancer cell line derived CSCs. CSCs were isolated from the breast cancer cell lines MCF-7 and MDA-MB-231 using a mammosphere assay. The effect of the A2BAR agonist BAY606583 on cell proliferation was evaluated using XTT and mammosphere formation assays, respectively. Apoptosis was assessed using Annexin-V staining and cell cycle analyses were performed using flow cytometry. The expression levels of Bax, Bcl-2, cyclin-D1, CDK-4 and (phosphorylated) ERK1/2 were assessed using Western blotting. Our data revealed that the breast cancer cell line derived mammospheres were enriched for CSCs. We also found that A2BAR stimulation with its agonist BAY606583 inhibited mammosphere formation and CSC viability. In addition, we found that the application of BAY606583 led to CSC cell cycle arrest and apoptosis through the cyclin-D1/Cdk-4 and Bax/Bcl-2 pathways, respectively. Notably, we found that BAY606583 significantly down-regulated ERK1/2 phosphorylation in the breast cancer cell line derived CSCs. From our results we conclude that A2BAR induces breast CSC cell cycle arrest and apoptosis through downregulation of the ERK1/2 cascade. As such, A2BAR may be considered as a novel target for the treatment of breast cancer.

Euphorbia species have been used in traditional medicine in many countries for the treatment of cancer. This article aims to evaluate the capability of a new lathyrane diterpene isolated from Euphorbia aellenii to induce apoptosis in the Caov-4 cell line to determine the underlying mechanism of its anticancer effects. A new 6(17)-epoxylathyrane diterpenes: aellinane from Euphorbia aellenii was evaluated for viability of Caov-4 cells by MTT method. Apoptosis induction by lathyrane diterpene was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. The Bcl2 and Bax protein content were detected by Western blot analysis. Finally, we employed the fluorescent ROS detection kit and fluorochrome JC-1 to determine ROS levels and loss of mitochondria membrane potential (ΔΨm) in Caov-4 cells, respectively. The results show that lathyrane diterpene has significant cytotoxic effect against Caov-4 cells. The IC50 value was 45 μM. Annexin V/propidium iodide (PI) staining and caspase-6 activity assay confirmed that lathyrane diterpene is able to induce apoptosis in Caov-4 cells. The results also demonstrate that lathyrane diterpene up-regulated Bax and down-regulated Bcl-2 proteins. Moreover, apoptotic effect of lathyrane diterpene was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). This study demonstrated that lathyrane diterpene has profound activity against Caov-4 cells. Analysis of apoptosis-related proteins revealed that lathyrane diterpene triggered the mitochondrion-mediated apoptosis pathway, which led to the loss of mitochondrial membrane potential (ΔΨm) and activation of caspase-6. Therefore, we believe that lathyrane diterpene might be a promising natural compound in ovarian cancer therapy.

Numerous studies have demonstrated the role of A3 adenosine receptor (A3AR) and signaling pathways in the multiple aspects of the tumor. However, there is a little study about the function of A3AR in the biological processes of cancer stem cells (CSCs). CSCs have a critical role in the maintenance and survival of breast cancer. The aim of current study was to investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). XTT assay showed antiproliferative effect of A3AR agonist (Cl-IB-MECA) on BCSCs. Our results also demonstrated that A3AR agonist reduces mammosphere formation in a dose-dependent manner. Flow cytometry analysis showed that A3AR agonist induces G1 cell cycle arrest and apoptosis in BCSCs. Western blot assay showed that A3AR agonist inhibits the expression of cell cycle and apoptotic regulatory proteins as well as the expression of ERK1/2 and GLI-1 proteins. Finally, these findings propose that A3AR agonist induces cell cycle arrest and apoptosis in BCSCs by inhibition of ERK1/2 and GLI-1 cascade. J. Cell. Biochem. 118: 2909-2920, 2017. © 2017 Wiley Periodicals, Inc.

Aim of the Study: The cell cycle, a vital process that involves in cells' growth and division, lies at the heart of cancer. It has been shown that IB-MECA, an A3 adenosine receptor agonist inhibits the proliferation of cancer cells by inducing cell cycle arrest in several tumors. In this study, we evaluated the role of IB-MECA inhibition in cell cycle progression in ovarian cancer cells. Materials and Methods: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in Caov-4 and OVCAR-3. Analysis of cell cycle distribution was carried out by flow cytometry. To determine the mechanisms of IB-MECA-mediated induction of cell cycle arrest, the expression of cell cycle regulatory proteins Cyclin D1 and cyclin-dependent kinase 4 (CDK4) was evaluated. Results: Our results showed that IB-MECA significantly reduced cell viability in a dose-dependent manner. Moreover, our results indicated that a low concentration of IB-MECA induced G1 cell cycle arrest. Reduction of Cyclin D1 and CDK4 protein levels was also observed after treating cancer cells with IB-MECA. Conclusion: This study demonstrated that IB-MECA induces G1 phase cell cycle arrest through Cyclin D1/CDK4-mediated pathway in ovarian cancer cells.

Natural products isolated from plants provide a valuable source for expansion of new anticancer drugs. Nardosinen (4,9-dihydroxy-nardosin-6-en) is a natural sesquiterpene extracted from Juniperus foetidissima. Recently, we have reported the cytotoxic effects of nardosinen in various cancer cells. The aim of the current study was to investigate the anticancer features of nardosinen as well as its possible molecular mechanisms of the nardosinen cytotoxic effect on breast tumor cells. MTT assay showed that nardosinen notably inhibited cell proliferation in a dose-dependent manner in MCF-7 breast cancer cells. The growth inhibitory effect of nardosinen was associated with the induction of cell apoptosis, activation of caspase-6, increase of reactive oxygen species (ROS), and loss of mitochondrial membrane potentials (ΔΨm). Western blot assay following treatment with nardosinen showed that the expression levels of the Bax were significantly up-regulated and the expression levels of the Bcl-2 were significantly down-regulated. Our results finally exhibited that nardosinen induces apoptosis in breast cancer cells via the mitochondrial and caspase pathways.

Objectives Breast cancer stem cells (CSCs) are a small population of tumour cells with the ability of self-renewal and resistance to chemotherapy. Targeting CSCs is a promising strategy for treatment of cancer. A recent study demonstrated that adenosine receptor agonists inhibit glioblastoma CSCs proliferation. At present, the effect of adenosine on breast CSCs has not been reported. Therefore, this study was designed to evaluate the effect of adenosine and its signalling pathways in breast CSCs. Materials and methods Anti-proliferative effect of adenosine on breast CSCs was evaluated by mammosphere formation and MTS assay. The effect of adenosine on cell cycle progression was examined using flow cytometry. Detection of apoptosis was conducted by Annexin V-FITC. The expression levels of cell cycle and apoptosis regulatory proteins as well as ERK1/2, and GLI-1 were measured by Western blot. Results Adenosine reduced CSCs population and mammosphere formation in breast CSCs. Adenosine induced G1 cell cycle arrest in breast CSCs in conjunction with a marked down-regulation of cyclin D1 and CDK4. Adenosine also induced apoptosis by regulation of Bax/Bcl-2 ratio, mitochondrial membrane potential depletion and activation of caspase-6. Moreover, adenosine inhibited ERK1/2 phosphorylation and GLI-1 protein expression. Conclusions These findings indicated that adenosine induces cell cycle arrest and apoptosis through inhibition of GLI-1 and ERK1/2 pathways in breast CSCs.

Numerous studies have demonstrated the role of A3 adenosine receptor (A3AR) and signaling pathways in the multiple aspects of the tumor. However, there is a little study about the function of A3AR in the biological processes of cancer stem cells (CSCs). CSCs have a critical role in the maintenance and survival of breast cancer. The aim of current study was to investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). XTT assay showed antiproliferative effect of A3AR agonist (Cl-IB-MECA) on BCSCs. Our results also demonstrated that A3AR agonist reduces mammosphere formation in a dose-dependent manner. Flow cytometry analysis showed that A3AR agonist induces G1 cell cycle arrest and apoptosis in BCSCs. Western blot assay showed that A3AR agonist inhibits the expression of cell cycle and apoptotic regulatory proteins as well as the expression of ERK1/2 and GLI-1 proteins. Finally, these findings propose that A3AR agonist induces cell cycle arrest and apoptosis in BCSCs by inhibition of ERK1/2 and GLI-1 cascade. J. Cell. Biochem. 118: 2909-2920, 2017. © 2017 Wiley Periodicals, Inc.

Induction of apoptosis in cancer cells can be a promising treatment method in cancer therapy. Naturally derived products had drawn growing attention as agent in cancer therapy. The main target of anticancer drugs may be distinct, but eventually, they lead to identical cell death pathway, which is apoptosis. Here, we indicated that britannin, a sesquiterpene lactone isolated from Asteraceae family, has antiproliferative activity on the MCF-7 and MDA-MB-468 human breast cancer cells. Annexin V/propidium iodide (PI) staining, Hoechst 33258 staining, and caspase-3/9 activity assay confirmed that britannin is able to induce apoptosis in MCF-7 and MDA-MB-468 cells. The Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to britannin treatment, while the expression of Bax protein was increased, which were positively correlated with elevated expression of p53. Moreover, britannin also increased reactive oxygen species (ROS) generation which in turn triggered the loss of mitochondrial transmembrane potential (ΔΨm) and the subsequent release of cytochrome c from mitochondria into cytosol. Taken together, these results suggest that britannin inhibits growth of MCF-7 and MDA-MB-468 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may potentially serve as an agent for breast cancer therapy.

Background and aim The conventional nasopalatine nerve block is commonly used to obtain anaesthesia in the anterior portion of the palate. The painful nature of this approach, however, has led investigators to seek alternative methods to obtain anaesthesia. Labial infiltration of the maxillary central incisors can be considered an effective anaesthetic approach for the anterior palate. Our study aimed to assess the anaesthetic effect of a modified labial infiltration method on the nasopalatine nerve. Materials and method A case-control clinical trial was done on 60 patients referring for extraction of maxillary incisors (mean age 44 years). The patients were divided into two groups of 30 people. For the first group, a primary conventional infiltration was given to each patient from a point between the maxillary canine and the lateral to obtain preliminary anaesthesia for the maxillary anterior labial area. The second or the control group was anaesthetised by conventional injection into incisive papilla. Two to three minutes afterwards, a labial infiltration approach was done and the amount of pain determined by OPS (objective pain score) was assessed. After five to six minutes the level of anaesthesia in the anterior palate was assessed in both groups by an explorer and recorded as pain-free, mild pain or severe pain. The sign test was used to statistically analyse the data (p

This study aimed to assess the demographic characteristics of peripheral giant cell granulomas (PGCGs) and central giant cell granulomas (CGCGs) in patients treated at our centers.This 12-year retrospective study was based on existing data. Files of patients from 1993-2004 with a definite diagnosis of PGCGs and CGCGs from the oral pathology departments of our universities were assessed. Information regarding age distribution, gender, the jaw involved, the presenting area of the lesion, surgical treatment, and recurrence was documented.During the study period, 204 patients with CGCGs were treated. The patients with CGCGs varied in age from 5 to 72 years, and the mean age patients was 23.72 years. Among these, 127 cases (62.87%) occurred in the second and third decades of life. One hundred thirty cases (63.75%) occurred in females and 74 (36.25%) in males. Ninety cases (44.1%) presented in posterior parts of the jaws. One hundred forty-four cases (70.58%) appeared in the mandible. Peripheral GCGs presented in 575 patients, who varied in age from 2 to 85 years with a mean age of 31.02 years. Among these, 297 cases (51.65%) occurred in females and 278 (48.34%) in males. Four hundred sixty-seven cases (81.2%) occurred in the first five decades of life, and 352 cases (61.21%) appeared in the mandible.Giant cell granulomas comprised 9.29% of oral lesions. Peripheral GCG lesions occurred more than 2 times more frequently than CGCGs. Central GCGs occurred about 2 times more frequently in females, whereas PGCGs had an equal prevalence in both genders (P.05). The mean age for patients with CGCGs was less than patients with PGCGs (P.05). Central GCGs involved the mandible approximately 2 times more frequently than the maxilla (P.05). However, when presenting in the maxilla, CGCGs most frequently presented in the area anterior to the canines (P.05). Peripheral GCGs involved the mandible approximately 1.5 times more frequently than the maxilla (P.05). Thorough curettage was the main treatment modality used. There were 9 cases (4.41%) of recurrence of CGCGs and 8 cases (1.39%) of recurrence of PGCGs documented during the follow-up period (ranging from 1-12 years).