Background Glucagon-like petide-1 (GLP-1) agonists such as liraglutide are widely employed in type 2 diabetes due to their glucose reducing properties and small risk of hypoglycemia. Recently, it has been shown that GLP-1agonists can inhibit breast cancer cells growth. Nonetheless, concerns are remained about liraglutide tumor promoting effects as stated by population studies. Material and Methods We evaluated the effects liraglutide on proliferation of MDA-MB-231 cells by MTT assay and then ATP-binding cassette (ABC) transporters expressions assessed by Real time PCR.

Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg

Hypoxia in the microenvironment is related to chemotherapy resistance, tumor progression, and metastasis. Curcumin, as a phenolic compound extracted from the turmeric, has been used as an anti-cancer agent with low toxicity in recent years. Since curcumin has inhibitory activities against hypoxia-inducible factors (HIFs) in several cancers, this study was conducted to examine the effect of curcumin on MCF-7 cells and cancer stem-like cells (CS-LCs) under hypoxic and normoxic conditions. CS-LCs were isolated from MCF-7 cells using the magnet activated cell sorting (MACS) method based on CD44 +/ CD24

Background: Despite its various clinical applications, cyclophosphamide (CP), an alkylating chemotherapeutic agent, has demonstrated numerous side effects, including genetic toxicity.Objectives: This study investigated the protective action of Origanum vulgare L., a powerful antioxidant plant, on the genotoxicity of CP in the mice blood lymphocytes.Methods: The mice were pre-treated orally with different doses of 50, 100, 200, or 400 mg/kg O. vulgare ethanolic extract once a day for 7 consecutive days. One hour after the final dose of O. vulgare, each animal received a single intraperitoneal administration of 200 mg/kg CP. After 24 hours, the preventive effect of O. vulgare was evaluated using an in vitro micronucleus (Mn) test in cytokines

Background: Despite its various clinical applications, cyclophosphamide (CP), an alkylating chemotherapeutic agent, has demonstrated numerous side effects, including genetic toxicity.Objectives: This study investigated the protective action of Origanum vulgare L., a powerful antioxidant plant, on the genotoxicity of CP in the mice blood lymphocytes.Methods: The mice were pre-treated orally with different doses of 50, 100, 200, or 400 mg/kg O. vulgare ethanolic extract once a day for 7 consecutive days. One hour after the final dose of O. vulgare, each animal received a single intraperitoneal administration of 200 mg/kg CP. After 24 hours, the preventive effect of O. vulgare was evaluated using an in vitro micronucleus (Mn) test in cytokines

Background: Green tea (Camellia sinensis), which is the most common drink across the world after water, has many antioxidant properties. Epigallocatecin-3-gallate (EGCG) is a flavonoid which accounts for 33–50% of green tea solids. It functions as a powerful antioxidant, preventing oxidative damage in healthy cells, with antiangiogenic and antitumor activities and as a modulator of tumor cell response to chemotherapy. Malathion is an organophosphate pesticide which is widely used in agriculture, veterinary and industries. Oxidative stress has been identified as one of malathion’s

Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage‐induced apoptosis are not well described. In the present study, we used etoposide‐induced DNA damage in MCF‐7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide‐induced DNA damage compared to wild‐type cells. However, FHIT knockdown blocked p53 expression

GDF15 plays a paradoxical role during carcinogenesis; it inhibits tumour growth in the early stages and promotes tumour cell proliferation in the late stages of cancer. Besides, GDF15 can induce apoptosis in some cancer cells including A549 but not in some others. Moreover, as a potential receptor for GDF15, TGFBR2 is inactivated during carcinogenesis in many types of cancers, and it is not present in cells with no GDF15 induced apoptosis. Thus, we tested whether GDF15 overexpression and/or TGFBR2 silencing can affect the GDF15 induced apoptosis in A549 cells. The full and mature forms of GDF15 were cloned and overexpressed in A549 cells. The TGFBR2 was silenced using specific siRNA and confirmed by real‐time PCR. Results indicated that

Background:The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo.Methods:In the present study, the inhibitory effect of WIN 55212-2 (a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous le

Benzo[α]pyrene (BaP) can have significant role in the development of breast cancer via aryl hydrocarbon receptor (AhR) activation. AhR activation has been studied in several functions such as survival, migration and invasion of cancer cells. In cancer, integrins contribute to the migration/invasion process and are regulated by nuclear factor of activated T cells (NFAT) and transforming growth factor (TGF) beta pathways. The aim of the present study was to examine the effect of BaP, an activator of AhR and cyclosporine A (CsA), as inhibitor of NFAT on migration and invasion of MDA‐MB‐231 cells. Furthermore, the effects of BaP and CsA were evaluated regarding the crosstalk of AhR, NFAT1 and TGF‐β receptor 1 signaling. Treatment of MD

Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated. Metabolic parameters implicated to the glucose and insulin statues such as homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance

AimsSepsis is a potentially fatal illness that can lead to impairment of multiple organs such as liver. The condition is deeply associated with oxidative stress and inflammation. Monomethyl fumarate (MMF) has manifested antioxidant and immunomodulatory properties. The aim of current study was to evaluate protective effects of MMF in sepsis-induced hepatic dysfunction.Main methodsSepsis was induced by cecal ligation and puncture (CLP). Wistar rats were assigned to one of sham, CLP, CLP + dexamethasone (as positive control of inflammation) and CLP + MMF groups. Levels of serum IL-1β, IL-6, IL-10, AST, ALT and γ‑GT were quantified. Furthermore, Hepatic levels of GSH and MDA and mRNA expression of TNF and NFKBIA along with hepatic p

Receptor tyrosine kinases (RTKs) are pharmaceutically attractive targets due to their fundamental role in tumor formation. The hallmark of pancreatic cancer is its high mortality rate attributed to the existence of cancer stem cell (CSC) subpopulations which result in therapy resistance and recurrence. c-Met is a known pancreatic CSC marker that belongs to the family of RTKs. To surmount the hurdles related to ligand-independent c-Met activation, we aimed to elucidate the inhibitory mechanisms of withaferin A (WA) and carnosol (CA) as two hit phytochemicals against c-Met kinase domain. Both tested compounds attenuated HGF-mediated proliferation across various established c-Met+ cancer cell lines and altered cell cycle distribution accompani

Background: Poisoning and drug overdoses are considered a health problem in moderncountries. In this study, we assessed the pattern of poisoning and drug overdoses at ImamKhomeini hospital in Sari city, the northern region of Iran. Methods: To assess the pattern and circumstances of poisoning, the patients’ informationwho were referred to the emergency unit with acute toxic poisoning over four years wererandomly obtained retrospectively from their medical records. Results: A total of 1,646 patients were analyzed. The highest rate of poisonings was related tosuicidal intentions and mostly occurred at age of 18 to 35 years and in females. Medicationswere the principal groups of poisons involved (53.15%), including benzodiazepines as themost

The underlying mechanisms for the neuroprotective effects of lithium chloride in neurodegenerative diseases such as seizures remain unknown. In present study the downstream signaling pathway of phospho-ERK/NMDA receptors/nitric oxide has been studied. For this purpose, acute and chronic effect of lithium in seizure animal model and the interaction of NMDA receptor antagonist (MK-801) and neuronal nitric oxide synthase (nNOS) inhibitor (7-NI) with these neuroprotection has been studied.Acute lithium administration showed pro-convulsive properties in pentylenetetrazole (PTZ)-induced seizure model while chronic treatment increased the seizure threshold significantly. The serum level of lithium in treated mice were 0.48 mEq/L corresponding the

Obesity is associated with higher postmenopausal breast cancer incidence. Visfatin level alteration is one of the mechanisms by which obesity promotes cancer. Ligand-independent activation of estrogen receptor alpha (ERα) is also associated with carcinogenesis. The activity of ERα is modulated through phosphorylation on multiple sites by a number of protein kinases. Here we investigated the effect of visfatin as a novel adipocytokine on the phosphorylation and activity of ERα in MCF-7 breast cancer cells. We showed that exogenous administration of visfatin significantly increased the phosphorylation of ERα at serine 118 (Ser118) and 167 (Ser167) residues. Visfatin-induced Ser118 phosphorylation was diminished after treatment of cells wi

Cyclosporin A (CsA) is known to have an immunosuppressive action. However, it is also attracting attention due to its effects on the nervous system, such as inhibiting the development and expression of morphine-induced tolerance and dependence through unknown mechanisms. It has been shown that CsA modulates the nitric oxide (NO) synthesis and extracellular signal-regulated kinases (ERK) activation, which are potentially involved in signaling pathways in morphine-induced tolerance in cellular models. Therefore, the current study was designed to evaluate the modulatory role of CsA on the MOR tolerance, by targeting the downstream signaling pathway of NO and ERK using an in vitro model. For this purpose, T98G cells were pretreated with CsA, ca