Evaluation of the inhibitory synergic effects of the Persian Gulf brittle star extract and taxol on ovarian cancer A2780cp

Paclitaxel is a current standard chemotherapeutic drug for ovarian cancer with several side effects. Recurrences of drug resistant clones have been considered the serious problem in the failure of chemotherapy. Medicinal marine natural products have been intensively proposed as diverse chemotherapeutic agents. Therefore there is an affinity to find efficient modality to overwhelm ovarian cancer chemo resistance complication. Here we examine whether brittle star extract as marine echinoderm natural resources can remarkably improve the cytotoxicity of paclitaxel in human ovarian cancer. MTT (dimethyl thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay, PI (Propodium Iodide) assay, DAPI (4', 6-diamidino-2-phenylindole) staining, Acridine orange staining, caspase-3 and caspase-9 were performed to investigate cytotoxic effect. We found that a combination of sub-toxic concentrations of brittle star methanolic extract (lower than IC_50) can significantly enhance ovarian cell growth inhibition and intrinsic apoptosis pathways induced by paclitaxel. Consequently a combination of paclitaxel and brittle star extract may offer novel innovative strategies for ovarian cancer chemotherapy

Preventive effect of vitamin B6 on developmental toxicity of carbamazepine in mice

Objective(s): Carbamazepine (CBZ) is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects (NTDs), growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice. Materials and Methods: Sixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal injection (IP) of 30 mg/kg (I) or 60 mg/kg (II) of CBZ on gestational days (GD) 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg (III) or 60 mg/kg (IV) of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X 2 test using SPSS software. Results: The mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations. Conclusion: This study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research

Cytotoxic and antioxidant effect of chrysin on neonate mouse spermatogenic stem cells

Background: So far, many plants have been used for the treatment of infertility. Several studies have revealed that chrysin (as an active metabolite) improves animals' reproduction. Therefore, the objective of this study was to evaluate the effect of chrysin on Balb/C mice spermatogenic stem cells. Materials and Methods: In this in vitro experimental study Balb/C neonate spermatogonia stem cells cultured in DMEM-F12 medium were treated with various concentrations of chrysin (2.5, 5, 10, 20, 40 µg/ml) for 6 and 12 days. Then the cytotoxicity was assessed using MTT, Akredin orange/Propodium Idid, DAPI and antioxidant concentration DCF-DA tests. Results: Chrysin showed no remarkable cytoxicity in concentrations less than 5 µg/ml. While, after 6 days the viability of cells treated with chrysin 10, 20 and 40 µg/ml was decreased to 30, 45 and 56 (P<0.05 and P<0.001, respectiely); after 12 days the viability of cells was decreased to 44, 56 and 65 (P<0.05, P<0.01 and P<0.001, respectiely). DCF-DA results revealed a 80 antioxidant capacity of chrysin in 5 and 2.5µg/ml concentrations. Conclusion: Lower concentrations of chrysin has protective effect on Balb/C mice spermatogenic through improving cell viability, decreasing cells apoptosis and inhibiting free radicals

Chitosan extracted from the Persian Gulf chiton shells: Induction of apoptosis in liver cancer cell line

Here for the first time, we investigated the cytotoxic effects of the chitosan extracted from the Persian Gulf Chiton shell (Acanthopleura vaillantii) on liver cancer cell line (HepG_2). Chitosan extraction was implemented following this method: chitin was produced by demineralization and deproteinization procedure, and the extracted chitin was converted into soluble chitosan using deacetylation method. The cytotoxic effects of extracted chitosan were evaluated using four different tests, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V-FITC, propidium iodide (PI) staining, 4',6-diamidino-2-phenylindole (DAPI) staining, and Caspase activity analysis. The IC_50 inhibitory concentrations of chitosan were obtained at 250 µg/mL after 24 h. Chitosan clearly inhibited the growth of hepatocarcinoma cells in vitro in a dose-dependent manner. For detecting the induced cell apoptosis, HepG_2 cells were treated with 125, 250 and 500 µg/ml of chitosan for 24 h. According to the result of Annex in V/PI kit, in 125, 250, and 500 µg/ml of chitosan, 28.2, 49.1, and 83.3% of HepG_2 cells undergone late apoptosis, respectively. The morphology of treated cells by DAPI staining showed non uniform plasma membrane and DNA fragmentation compared to untreated cells with perfect nucleus. The analysis of cell cycle using flow cytometry demonstrated that the rate of sub-G1 peak was increased to 52.7%. Both caspase-3 and -9 activities increased by the extracted chitosan, but it was only significant for caspase-3. The results of the present study suggested that the extracted chitosan has efficient cytotoxicity on HepG_2 cells. Therefore, the extracted chitosan from the shell of the Chiton may be considered as a futuristic natural product regarding the treatment of liver cancer

The synergistic influence of Holothuria arenicola extract and imidazole carboxamide on Cellosaurus cell line B16-F10

Skin cancer has been reported as a contemporary malignant cancer. Here, anti-cancer effects of sea cucumber extract (SCE) from Holothuria arenicola have been examined on melanoma cells and compared with imidazole carboxamide (Dacarbazine) as a chemotherapy medication against melanoma and Hodgkin's lymphoma. MTT assay and morphological analysis were performed to evaluate cytotoxic effects of H. arenicola extract. Also, several methods were exerted to detect cell dying by SCE and imidazole carboxamide. The MTT assay showed that B16F10 cells proliferation was blocked by SCE (IC_50=31µg ml ^-1) and imidazole carboxamide (IC_50=1600 µg ml ^-1) in a dose and time dependent manner. Apoptosis induction yield treatment occurred at IC50 concentration of SCE and imidazole carboxamide using DAPI staining, Acridine orange/Propodium iodide, PI flow cytometry and annexin/PI assay. The caspase colorimetric kit indicated that SCE and imidazole carboxamide could induce apoptosis through an intrinsic pathway. Collectively, our findings suggested that the methanolic SCE has more efficient cytotoxicity efficiency compared to imidazole carboxamide. Therefore, SCE may be considered as a futuristic marine natural product regarding prevention or treatment of melanoma malignancy

Angiotensin-converting enzyme inhibitor, Enalapril, inhibits tumor growth and potentiates the antitumor efficacy of 5-FU in colorectal cancer

OBJECTIVE: Colorectal cancer (CRC) is among the leading causes of cancer-related death, indicating the need for the identification of novel therapeutic approaches to increase the activity of current therapy or have better efficacy. Angiotensin-converting enzyme (ACE) is being reported to be associated with aggressive behaviors of CRC cells and poor prognosis. Here we explored the therapeutic potency of targeting ACE by Enalapril in CRC in vivo model. MATERIALS AND METHODS: A xenograft model of CRC was used to investigate the effects of Enalapril alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin and Eosin and Masson trichrome staining) and biochemical studies of Malondialdehyde (MDA), total thiols, superoxide dismutase (SOD) and catalase (CAT) activities. RESULTS: Enalapril reduced tumor growth and increased tumor necrosis; this effect was more pronounced in Enalapril plus 5-FU combination. Enalapril/5-FU was able to decrease tumor fibrosis and collagen content. ACE inhibitors also increased MDA level, as an oxidative stress marker, while reducing total thiol group levels, SOD and CAT enzyme activity. CONCLUSIONS: Our findings provide a novel insight on the therapeutic potential targeting of the renin–angiotensin system as a new therapeutic option in combination with current therapeutic agents 5-FU in the treatment of CRC

Effect of Curcumin on Angiogenesis in Aortic Ring Model of the Wistar Rat

Introduction: Tumeric is a plant with both food and medical properties by which Curcumin is derived from. It has various pharmacological effects. Angiogenesis, a dynamic process of endothelial cells proliferation in order to develop new blood vessels from the previous ones, affects a wide range of physiological and pathological processes such as tumor growth and metastasis. In this study, anti angiogenic effects of Cucumin were investigated in aortic ring of Wistar rats. Methods: In this experimental study, Aortic ring was cut up in to 1 mm pieces and cultured in collagen matrix. After three days, sprouting angiogenesis were observed, and then aortic rings were treated with Curcumin at concentration of 25, 50 and 100 µg/ml. Effects of treatment in all cases were photographed and then investigated by invert microscope. Lengths of vessels were measured by Image J software. Moreover, the study data were analyzed using SPSS in significant level of P0.05).In fact, average length and number of blood vessels in experimental group 1 demonstrated no significant difference compared with control group, though in the experimental group 2 (79.45±3.2mm), (12±1.3) and 3 (38.93±1.1mm), (8±1.1) significant differences were observed (P<0.05(. Conclusion: The results proposed that the Curcumin had dose-dependent inhibitory effects on angiogenesis in rat aortic ring Therefore, it can be introduced as an appropriate candidate in order to study angiogenesis and related diseases

Comparison of the Percentages of Peripheral Blood CD4+ CD25+ T Lymphocytes in Recurrent Abortion and Normal Pregnancy

Abstract: Background & Aims: Recent evidences indicate that parts of the immunoregulation system such as CD4+CD25+Tcells (Treg) and Th2 cells and Th1 cells, play very important roles in the maintenance of pregnancy. The deficiency in proper recognition of fetal alloantigen by the maternal immune system is associated with recurrent pregnancy failure. Here, we investigate the proportional changes of CD4+CD25+Tcells in peripheral blood of women with unexplained recurrent spontaneous abortion in comparison to women with normal pregnancy by using flowcytometry. Methods: The case group was comprised of 24 women who had at least three successive miscarriages with unexplained etiology. They had normal karyotypes, anticardiolipin and prolactin and their husbands had normal spermograms. The percentages of TCD4+CD25+cells in peripheral blood of these patients were compared with those of 21 women who had normal pregnancy with no history of pregnancy loss. Anti-CD4, anti-CD25 and anti-CD3 antibodies were added to lymphocytes isolated from peripheral blood. Then samples were incubated, centrifuged and washed. Finally cells were analyzed using FACS Caliber system and data of the two groups were compared. Results: Mean percentage of CD4+CD25+bright T cells in peripheral blood in case group was significantly lower compared to the control group (P=0.000). Mean percentage of CD4-CD25 bright cells in the CD4+Tcell peripheral blood was significantly higher in case group campared to the control group (P=0.021). Conclusion: Decrease of CD4+CD25 bright T cells plays a major role in tolerating conceptus antigens and cytokine and might contribute to the maintenance of pregnancy. Inadequate CD4+CD25+Tcells or their functional deficiency may link with miscarriage. Therefore, alteration of CD4+CD25+T cells can be used as an immunologic marker for monitoring of patients with unexplained recurrent spontaneous abortion. Keywords: Recurrent abortion, CD4+CD25+ T cells, Flowcytometr