Gaillardin inhibits autophagy and induces apoptosis in MCF-7 breast cancer cells by regulating JAK/STAT pathway.

BACKGROUND: Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi. AIM: The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line. METHODS: The MTT assay was used to unravel the antiproliferative effects of gaillardin on MCF-7 cells. The expression of apoptosis-related genes including CASP3, BAX, BCL2, STAT3, and JAK2, and key markers of autophagy such as ATG1, ATG4, ATG5, ATG7, ATG12, BECN1, and MAP1LC3A were measured by real time-PCR method. The protein expression of Caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III was determined using western blotting. RESULTS: Gaillardin treatment significantly decreased the proliferation of MCF-7 cells with a parallel upregulation of the level of pro-apoptotic caspase-3 enzyme with no effect on Bax and Bcl2 expression. The levels of phosphorylated and active forms of JAK2 and STAT3 proteins were reduced following the treatment of MCF-7 cells with gaillardin. This sesquiterpene lactone com-pound considerably downregulated the levels of six autophagy markers, including ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III in MCF-7 cells. CONCLUSION: These data indicated the apoptosis-inducing activity of gaillardin in MCF-7 cells by a mechanism that inhibits the JAK/STAT signaling pathway. Further, autophagy inhibition was the other phenomenon caused by gaillardin in MCF-7 cells. These results can provide evidence to highlight the role of gaillardin as a novel therapeutic for the treatment of breast cancer.

Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.

Britannin a Sesquiterpene Lactone from Inula aucheriana Exerted an Anti-leukemic Effect in Acute Lymphoblastic Leukemia (ALL) Cells and Enhanced the Sensitivity of the Cells to Vincristine.

Since chemotherapy drugs have dose-related side effects, there is still a need for finding new agents with suitable cytotoxic effects without any harmful effects. For this purpose, we evaluated the cytotoxic effects of Britannin that is a Sesquiterpene Lactone compound Inula aucheriana, alone or in combination with Vincristine (VCR), on Acute Lymphoblastic Leukemia (ALL)-derived MOLT-4 cells. In this study, we found that Britannin decreased the viability of MOLT-4 cells with the IC50 Values of 2 µM, but had no cytotoxic effects on normal cells or Peripheral Blood Mononuclear Cells (PBMCs). Our results also showed that Britannin decreased the proliferation of MOLT-4 cells by preventing the transition of the cells from the S phase of the cell cycle through the up-regulation of p21 and p27. Moreover, this agent induced ROS-mediated apoptosis by altering the expression of Bax, Bim, Caspase3, Bcl2, and XIAP. Britannin also produced a synergistic effect with Vincristine in MOLT-4 cells. Taken together, the results of this study showed for the first time that Britannin, as a natural Sesquiterpene Lactone, has cytotoxic effects that could be considered as an anti-leukemic agent in the treatment of ALL. However, there is still a demand for further studies that examine the efficacy and the safety of this purified compound.

Britannin, a sesquiterpene lactone induces ROS-dependent apoptosis in NALM-6, REH, and JURKAT cell lines and produces a synergistic effect with vincristine.

BACKGROUND: Britannin, a Sesquiterpene Lactone isolated from Inula aucheriana, has recently gained attraction in the therapeutic fields due to its anti-tumor properties. This study was designed to evaluate the effect of this agent on Acute Lymphoblastic Leukemia (ALL) cell lines, either as a monotherapy or in combination with Vincristine (VCR). METHODS AND RESULTS: To determine the anti-leukemic effects of Britannin on ALL-derived cell lines and suggest a mechanism of action for the agent, we used MTT assay, Annexin-V/PI staining, ROS assay, and real-time PCR analysis. Moreover, by using a combination index (CI), we evaluated the synergistic effect of Britannin on Vincristine. We found that unlike normal Peripheral Blood Mononuclear Cells (PBMCs) and L929 cells, Britannin reduced the viability of NALM-6, REH, and JURKAT cells. Among tested cells, NALM-6 cells had the highest sensitivity to Britannin, and this agent was able to induce p21/p27-mediated G1 cell cycle arrest and Reactive Oxygen Specious (ROS)-mediated apoptotic cell death in this cell line. When NALM-6 cells were treated with Nacetyl-L-Cysteine (NAC), a scavenger of ROS, Britannin could induce neither apoptosis nor reduce the survival of the cells suggesting that the cytotoxic effect of Britannin is induced through ROS-dependent manner. Moreover, we found that a low dose of Britannin enhanced the effect of Vincristine in NALM-6 cells by inducing apoptotic cell death via altering the expression of apoptotic-related genes. CONCLUSIONS: Overall, our results proposed a mechanism for the cytotoxic effect of Britannin, either as a single agent or in combination with Vincristine, in NALM-6 cells.

Antiproliferative Effect of Gaillardin from Inula oculus-christi in Human Leukemic Cells.

Gaillardin (GLN) is a sesquiterpene lactone isolated from the chloroform extract of Inula oculus-christi L. This natural compound has shown cytotoxicity in various cancerous cell line. However, its effect on leukemic cells is ambiguous. Due to the neurotoxicity of vincristine (VCR) in acute lymphoblastic leukemia (ALL), we aimed to examine the cytotoxic effects of GLN alone and in combination with vincristine on induction of apoptosis, and cell cycle progression in ALL cell lines (NALM-6 and MOLT-4). Our results displayed that GLN could induce cytotoxic effects in MOLT-4 and NALM-6 with IC50 values of 7.3 and 6.1 µM, respectively. In this study, we demonstrated that GLN induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose-dependent manner. Fortunately, this natural compound did not show significant cytotoxic effects on normal cells. This study demonstrated that GLN was capable to extend chemotherapeutic sensitivity in ALL cells by reducing VCR concentration without constraining its effectiveness. Therefore, it might act as a promising anticancer agent for the treatment of leukemia.

Britannin, a sesquiterpene lactone, inhibits proliferation and induces apoptosis through the mitochondrial signaling pathway in human breast cancer cells.

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.

Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines : Gaillardin-induced apoptosis in breast cancer cell lines.

Medicinal plant extracts have been widely used for cancer treatment. Gaillardin is a natural sesquiterpene lactone that has recently been reported to have anticancer properties. The ability to induce apoptosis is an important property of a candidate anticancer drug, which discriminates between anticancer drugs and toxic compounds. The current study was therefore carried out to address the issue if Gaillardin is able to induce apoptosis in the breast cancer cell lines MCF-7 and MDA-MB-468 and to determine the underlying mechanism of its anticancer effects. Apoptosis induction by Gaillardin treatment was confirmed by annexin V-FITC/PI staining, and caspase-3,-6, and-9 activation. Using Western blot analysis, we found that Gaillardin upregulated the pro-apoptotic protein Bax and p53 and downregulated the anti-apoptotic protein Bcl-2. Moreover, the apoptotic effect of Gaillardin was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). Taken together, these results demonstrate that Gaillardin can inhibit proliferation of breast cancer cells via inducing mitochondrial apoptotic pathway and therefore, might be a promising molecule in cancer chemoprevention or chemotherapy.

Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.

Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin) and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) µg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies.

Natural sesquiterpen lactones as acetylcholinesterase inhibitors.

Background and the purpose of the study: The amount of elder people who suffer from Alzheimer disease is continuously increasing every year. Cholinesterase inhibitors have shown to be effective in alleviating the symptoms of the disease, thus opening a field of research for these treatments. Herbal products, owning a reputation as effective agents in many biological studies are now drawing attention for inhibiting acetylcholinesterase, in other words, Alzheimer disease. In the present study, the ability of three sesquiterpene lactones from Inula oculus-christi and I. aucheriana to inhibit AChE has been evaluated through Ellman assay. Materials and Methods: Gaillardin and pulchellin C were obtained from I. oculus-christi and britannin from I. aucheriana by chromatographic methods. They were dissolved in methanol in concentration of 3 mg/mL and the AChEI activity of the compounds was determined by Ellman method using Acethylthiocholine iodide as the substrate and 5, 5'-dithiobis-2-nitrobenzoic acid as the reagent, in 96-well plates at 405 nm. Results: AChEI activity of the examined compounds was obtained as 67.0, 25.2 and 10.9% in concentration of 300 µg/L for gaillardin, britannin and pulchellin C, respectively. Conclusion: Among the three sesquiterpene lactones, gaillardin with 67% inhibition of AChE could be considered a good candidate for future Alzheimer studies.

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.

Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis. Sesquiterpene lactones are one of the large and diverse groups of planet-derived phytochemicals that can be used as sources for a variety of drugs. Some sesquiterpene lactones possess many biological activities such as anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic. This review article briefly overviews the intrinsic and extrinsic pathways of apoptosis and the interactions between the modulators of both pathways. Also, the present review summarizes the potential effects of sesquiterpene lactones on different modulators of the intrinsic and extrinsic pathways of apoptosis in a variety of cancer cell lines and animal models. The main purpose of the present review is to give a clear picture of the current knowledge about the pro-apoptotic effects of sesquiterpene lactones on various cancers to provide future direction in cancer therapeutics.

Targeting PPARγ/ NF-κB Signaling Pathway by Britannin, a Sesquiterpene Lactone from Inula aucheriana DC., in Gastric Cancer.

BACKGROUND: Gastric cancer is one of the most common and deadliest malignancies in the world. Therefore, there is an urgent need to develop new and effective agents to reduce mortality. The plants of genus Inula have gained the attention of researchers worldwide as a rich source of potent medicinal compounds. OBJECTIVE: This study explores the anti-cancer activity of Britannin, a sesquiterpene lactone isolated from Inula aucheriana DC., and its molecular mechanism in gastric cancer cells, AGS and MKN45. METHODS: Cytotoxicity was evaluated through the MTT assay following 24 h, 48 h, and 72 h treatment with different concentrations of Britannin. Apoptosis rate and caspase-3 activity were measured 24 h after treatment by Britannin. . Western blotting was performed to determine the expression of the NF-κB, IκBα, and PPARγ proteins. Moreover, quantitative RT-PCR was applied to measure the expression of NF-κB target genes. RESULTS: We showed that Britannin induced cell growth inhibition and apoptosis in gastric cancer cells. Britannin caused an elevation in mRNA and protein levels of PPARγ. The involvement of PPARγ was more confirmed using GW9662, a PPARγ inhibitor. Suppression of NF-κB was demonstrated by western blot analysis. Down-regulation of MMP-9, TWIST-1, COX-2, and Bcl-2 and up-regulation of Bax were also observed in gastric cancer cells. CONCLUSION: These results imply that activation of the PPARγ signaling pathway through suppression of NF-κB underlies the anti-cancer properties of Britannin in gastric cancer. Therefore, Britannin could be considered as a promising anti-cancer candidate for further evaluation.

Gene Ontology Assessment of Indirect Cold Physical Plasma and UV-Radiation Molecular Mechanism at the Cellular Level.

Introduction: The development of therapeutic methods implies an understanding of the molecular mechanism of the applied methods. Due to the widespread use of UV radiation and cold physical plasma in medicine, the molecular mechanism of these two methods is compared via gene ontology. Methods: Data were derived from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) which discriminate the cells treated with UV radiation versus indirect cold physical plasma were analyzed via gen ontology enrichment. The related biochemical pathways were extracted from the "Kyoto Encyclopedia of Genes and Genomes" (KEGG). Results: Among the 152 queried DEGs, 18 critical genes including SOC1, LDLR, ALO5, PTGS2, TNF, JUNB, TNFRSF1A, CD40, SMAD7, ID1, SMAD6, SERPINE1, PMAIP1, MDM2, CREB5, GADD45A, E2F3, and ETV5 were highlighted as the genes that victimize the two methods. Conclusion: NOTCH1 and TNF as the main genes plus SEREPINE1, KLF, and BDNF were introduced as the significant genes that are involved in the processes which discriminate cold physical plasma administration and UV-radiation as the two evaluated therapeutic methods.

Long and Short-terms Effects of Ablative Fractional Laser Therapy on Human Skin: A Network Analysis.

Introduction: Time-dependent effects of laser radiation have been investigated by researchers. An understanding of the molecular mechanism of the time course effect of the laser needs molecular assessment and function evaluation of the related genes. In the present study, the importance of repetition of treatment after 4 weeks and gene expression alteration after 7 days of laser radiation versus one day on the human skin was evaluated via protein-protein interaction (PPI) network analysis and gene ontology enrichment. Methods: The differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus (GEO) and assessed via PPI network analysis. The critical DEGs were enriched via gene ontology. The related biological processes and biochemical pathways were retrieved from "GO-Biological process" and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) respectively. Results: The repetition of laser therapy after 4 weeks of the first treatment did not have a significant effect on treatment efficacy. Sixty-three significant DEGs and six classes of biological terms discriminated the samples seven days after the treatment from individuals one day after the treatment. The studied DEGs were organized into two clusters with certain functions. Conclusion: Based on the findings after laser therapy, several days are required to complete the critical processes such as DNA biosynthesis and skin cornification.

Efficacy Evaluation of Human Skin Treatment with Photodynamic Therapy in Actinic Keratoses Patients.

Introduction: Photodynamic therapy (PDT) is a combined method of light and light-activated chemicals that are called photosensitizers (PSs). PDT is recommended as a high cure rate method with fewer side effects and a noninvasive tool to treat cancer. This study aimed to evaluate PDT efficacy as a therapeutic method against actinic keratoses in patients via protein-protein interaction (PPI) network analysis by using the gene expression profiles of Gene Expression Omnibus (GEO). Methods: Twenty-one gene expression profiles were extracted from GEO and analyzed by GEO2R to determine the significant differentially expressed genes (DEGs). The significant DEGs were included in PPI networks via Cytoscape software. The networks were analyzed by the "Network Analyzer", and the elements of the main connected components were assessed. Results: There were three main connected components for the compared sets of the gene expression profiles including the lesional region of skin before (Before set) and after (After set) PDT versus healthy (healthy set) skin and before versus after. The before-health comparison showed a partial similarity with the After-Healthy assessment. The before-after evaluation indicated that there were not considerable differences between the gene expression profile of the lesional region before and after PDT. Conclusion: In conclusion, PDT was unable to return the gene expression pattern of the actinic keratoses skin to a healthy condition completely.

Assessment of Photosensitizer Concentration Effects on the Efficacy of Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) is an attractive approach in medicine. Due to its noninvasive nature and low side effects, PDT has been developed quickly. In the present study, the gene expression profiles of the human cell line that was treated via PDT in the sub-lethal concentration (LC50) and super-lethal concentration (LC90) of a photosensitizer (PS) from Gene Expression Omnibus (GEO) were extracted and the common differentially expressed genes (DEGs) were investigated. Methods: The gene expression profiles of the treated cells were compared with a control, and the common DEGs were determined. The common DEGs were assessed via protein-protein interaction (PPI) network analysis, and gene ontology enrichment was evaluated. The related biological terms for the common genes were identified. Results: Ninety-four common DEGs were selected to be analyzed. It appeared that the activation and increment of gene expression were prominent processes. Jun, Dusp1, Atf4, and Atf3 as four critical genes were highlighted. "Chromosomal and microsatellite instability in colorectal cancer" was identified as the main class of biological terms related to the assessed DEGs. Conclusion: The major molecular events which happened in both analyses indicated that PDT, independent from the concentration of PS, induced gross molecular changes such as the upregulation of Jun and Dusp1.

Collagen Synthesis as a Prominent Process During the Interval between Two Laser Sessions.

Introduction: Many people suffer from skin photodamage, especially photoaging. The application of a laser to repair damages is a common therapeutic method that is used widely. In the present study, the effectiveness and molecular mechanism of an Er:Glass non-ablative fractional laser on the human skin was assessed via bioinformatics and network analysis. Methods: The gene expression profiles of 17 white female forearm skins which received an Er:Glass non-ablative fractional laser before and after laser treatment in two sessions were extracted from Gene Expression Omnibus (GEO). Data were evaluated via GEO2R and the significant differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis. The central nodes were identified and discussed for the compared set of samples. Results: Five classes of samples were clustered in two categories: first, baseline, 7 and 14 days after the first session of laser treatment, and second, one day after the first laser session, 29 days after the first laser session, and 1 day after the second laser session. The gross cell functions such as cell division and cell cycle and immune response were highlighted as the early affected targets of the laser. Collagen synthesis was resulted after the first laser session. Conclusion: In conclusion, the time interval between laser sessions plays a critical role in the effectiveness of laser therapy. Findings indicate that the gross effect of laser application appears in a short time, and important processes such as collagen synthesis happen later.

Introducing Critical Genes in Response to Photodynamic Therapy: A Network Analysis.

Introduction: Photodynamic therapy (PDT) is applied as an efficient method for preventing the progress of cancers. Light and a photosensitive compound which is known as photosensitizer (PS) are the main parts of PDT. In the present study, molecular events after using PDT in the presence of a super lethal dose of a PS were assessed via protein-protein interaction (PPI) analysis. Methods: Data were extracted from Gene Expression Omnibus (GEO). The gene expression profiles of the treated human Sk-Cha1 cells via PDT were compared with the control cells. Expressed change analysis and PPI network analysis were administrated via Cytoscape software v 3.7.2 to find the critical differentially expressed genes (DEGs). Regulatory relationships between the central DEGs were evaluated and the highlighted genes were identified. Results: The significant amounts of gene expression values were grouped and a few DEGs characterized by tremendously expressed values were identified. EGFR, CANX, HSPA5, MYC, JUN, ITGB1, APP, and CDH1 were highlighted as hub-bottleneck DEGs. EGFR, CDH1, and JUN appeared as a set of SEGs, which play a crucial role in response to PDT in the treated Sk-Cha1 cells. Conclusion: In conclusion, regulatory relationships between EGFR, CDH1, and JUN, which have an effect on the regulation of cellular survival, differentiation, and proliferation, were highlighted in the present investigation.

Extracellular matrix is the main targeted environment in early stage of pancreatic ductal adenocarcinoma.

Aim: Due to weak diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC), detection of PDAC possible biomarkers in early stage is the main aim of this study. Background: PDAC is known as an exocrine cancer with a 5-year overall survival of 11%. Methods: Gene expression profiles of early stage of PDAC tissue and normal tissue are downloaded from gene expression omnibus (GEO) and evaluated via GEO2R. The significant differentially expressed genes (DEGs) are investigated via protein-protein interaction (PPI) network analysis and gene ontology. Results: Among 104 DEGs, ALB, COL1A1, COL1A2, MMP1, POSTN, PLAU, and COL3A1 were pointed out as hub nodes. "Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13" group of 52 biological terms were identified as the main affected terms. Conclusion: In conclusion, ALB, MMP1, and COL1A1 genes were highlighted as possible biomarkers of early stage of PDAC. Dysfunction of extracellular matrix was identified as a main event in patients.

Assessment of the Response of Human Umbilical Vein Endothelial Cells to Photodynamic Therapy: Highlighting the Role of Il-17 Signaling Pathway.

Introduction: Photodynamic therapy (PDT) is a method based on the application of a photosensitive agent and the administration of light irradiation on the treated samples. PDT is applied as an effective tool with minimal side effects against tumor tissues. This study aimed to assess the targets of critical genes by PDT at the cellular level of cancer to provide a new perspective on its molecular mechanism. Methods: To assess the effect of PDT, we extracted the differentially expressed genes (DEGs) from the gene expression profiles of human umbilical vein endothelial cells (HUVECs) treated with PDT from Gene Expression Omnibus (GEO) databases. The queried DEGs were evaluated via a regulatory network and gene ontology enrichment to find the critical targets. Results: Among 76 queried significant DEGs, 27 individuals were interacted by activation, inhibition, and co-expression actions. Thirty DEGs were related to the five classes of biological terms. The IL-17 signaling pathway and PTGS2, CXCL8, FOS, JUN, CXCL1, ZFP36, and FOSB were identified as the crucial targets of PDT. Conclusion: PDT as a stimulator of gene expression and an activator of gene activity overexpressed and hyper-activated many genes. It seems that PDT introduces a number of genes and pathways that can be regulated by anticancer drugs to fight against cancers.

Introducing Albumin and Interleukin 6 as Common Critical Dysregulated Proteins Between Migraine and Gliosarcoma.

Introduction: It is reported that migraine may be a risk factor for brain cancers. Since one of the best ways to assess this possible relationship is to study the molecular mechanism, here the common central dysregulated proteins between these diseases are investigated via network analysis. Methods: The dysregulated proteins of migraine and gliosarcoma are extracted from the STRING database and interacted via Cytoscape software, version 3.7.2. to form two separate networks. Central nodes of the networks are compared to find the common central district proteins. First neighbors of the common central proteins are studied. Results: The number of 11 hub bottlenecks was identified for each of the migraine and gliosarcoma cancer networks. Albumin (ALB) and interleukin 6 (IL6) were introduced as common differentially expressed central proteins. Kininogen 1 (KNG1), vascular endothelial growth factor A (VEGFA), and neurofibromatosis type I (NF1) the first neighbors of ALB-IL6 were connected to the central nodes of networks of the two studied diseases. Conclusion: ALB and IL6 can be considered molecular links between migraine and brain cancers. Highlights: Differentially expression of albumin (ALB) and interleukin 6 (IL6) is highlighted as the common key events in migraine and gliosarcoma.Kininogen 1 (KNG1), vascular endothelial growth factor A (VEGFA), and neurofibromatosis type I (NF1) are introduced as possible critical players in migraine and gliosarcoma.Based on four centrality parameters, ALB is characterized with stronger centrality properties relative to IL6. Plain Language Summary: Migraine is considered as a possible risk factor for brain cancers. Therefor exploring of relationship between brain cancers and migraine is attracted attention of researchers. Understanding of diseases molecular mechanism is an important tool to better diagnosis and therapy of the studied disorders. In the present study, the common features of molecular events in migraine and gliosarcoma are studied based on protein expression changes. Analysis indicates that a few numbers of proteins play critical roles in migraine and gliosarcoma. ALB, IL6, KNG1, VEGFA, and NF1 are highlighted as the key proteins which are dysregulated in the two studied diseases. Prominent role of ALB in development of cancers is pointed out by several researchers. Important role of IL6 in promotion of migraine is disused in the previous documents. Since some diseases are risk factors for the other disorders, understanding the common features of two diseases can provide suitable therapeutic protocol to prevent development of diseases. Our finding can be used to provide suitable procedure to prevent conversion of migraine to brain cancer.