Effects Of Noscapine Research Articles

Insan akciğer hücre hatlarında noskapinin antianjiogenik ve apopitotik etkileri

Objective: Lung cancer, one of the most important health problems today, is the most common type of cancer that causes death in both women and men.
 Although A549 lung cells originating from human alveolar carcinoma cells match the type II alveolar cell phenotype, it also has many characteristics that human primary alveolar epithelial cells have.
 Noscapine consists of the components in the poppy somniferum (opium). It was first isolated from Papaver somniferum (opium) in 1817. It consists of the most abundant opioids found in the opium plant (up to 10% of the total composition) after morphine. It is also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane, and S is an (-) isomer with R stereochemistry (S stereochemistry in phthalid-carbon and R in isoquinoline-carbon). Noscapine is structurally and chemically different from other opium alkaloids such as morphine, codeine, thebaine, papaverine and narcein.The aim of the study the ınvestıgatıon of the apoptotıc and antıangıogenıc effects of noscapine ın human lung cancer (A549) cells.
 Materials and Methods: In the study, concentrations of 10 ppm, 15 ppm, 20 ppm, 25 ppm, 40 ppm, 50 ppm, 60 ppm, 65 ppm, 70 ppm, 75 ppm, 80 ppm, 90 ppm and 100 ppm were used in the proliferation experiment proportion of vitality values. It was observed that it decreased and the LD50 value was determined as 40 ppm. Statistical analysis used: Statistical analysis of the analyzes was performed using SPSS Statistics 20,0 program.
 Results: VEGF values decreased at 20 ppm, 40 ppm and 80 ppm noscapine concentrations compared to the control group. There was a significant decrease in PARP values at 80 ppm.
 Conclusions: As a result of the findings; It is thought that concentrations of noscapine 10 ppm, 20 ppm and 40 ppm can reduce angiogenesis and prevent metastasis by lowering VEGF levels. PARP levels decreased at all noscapine concentrations but the most significant difference was seen at 80 ppm noscapine concentration.

Down-regulation of liver-intestine cadherin enhances noscapine-induced apoptosis in human colon cancer cells

ABSTRACTBackground: The aim of the present study was to explore the signaling pathway of noscapine which induces apoptosis by blocking liver-intestine cadherin (CDH17) gene in colon cancer SW480 cells.Methods: Human colon cancer SW480 cells were transfected with CDH17 interference vector and treatment with 10 µmol/L noscapine. The proliferation and apoptosis of SW480 cells were detected by MTT assay and AnnexinV-FITC/PI flow cytometry kit (BD), respectively. Cell invasion were assessed by transwell assays. Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot.Results: Compared to the noscapine group, the proliferation was decreased significantly and the apoptosis was increased significantly in SW480 cells of the siCDH17+noscapine group. Cyt-c and Bax protein levels in siCDH17+noscapine group was higher than that of the noscapine group, but Bcl-2 and Bcl-xL protein levels in siCDH17+noscapine group were lower than that of the noscapine group. Moreover, up-expression of CDH17 inhibited the efficacy of noscapine-induced apoptosis in SW480 cells.Conclusions: We inferred that down-expression of extrinsic CDH17 gene can conspicuously promote apoptosis-inducing effects of noscapine on human colon cancer SW480 cells, which is a novel strategy to improve chemotherapeutic effects on colon cancer.

Abstract 2619: Synergistic anticancer effect of Noscapine and Camptothecin is mediated through apoptosis and cell cycle arrest in A549 lung cancer

Abstract Background: The aim of this study was to evaluate the anticancer activity of a natural product Noscapine (Nos) and Camptothecin (CMP) combination (Nos+CMP) against non-small cell lung cancer (NSCLC) and to elucidate the underlying mechanism of action. Methods: A549 cells were treated with Nos, CMP or their combination and combination index (CI) values were calculated using isobolographic method. The apoptotic proportion of the cells and cell cycle effects were analyzed using flow cytometry. The expression of apoptotic proteins was detected by western blot analysis such as anti-apoptotic protein Bcl2, cell survival marker survivin, extracellular matrix proteins like MMP-2, MMP-9 and cell cycle regulatory proteins like p21 and cyclin dependent kinase 2 (CDK2). Results: The CI values (<0.61) were suggestive of synergistic behavior between Nos and CMP. To investigate the underlying mechanism of the Nos antiproliferative effect, cell cycle-analysis was conducted with A549 cells. Nos+CMP treatment group induced G2/M phase arrest (using the the fluorescence-activated cell sorting analysis) and the number of apoptotic cells were also increased significantly in a dose-dependent manner compared to Nos and CMP alone and control treatments. Furthermore, western blot analysis revealed that Nos+CMP treatment significantly upregulated 0.9 fold (p<0.05) the expression of tumor suppressor protein p21 Waf1/Cip1 (suggesting inhibition of cell cycle progression) compared to single agent treated and control groups. Expression of CDK2 (an important component of cell machinery) and cyclin D1 (another important regulator of cell cycle progression) was significantly downregulated 1.03 fold (p<0.05) and 0.7 fold (p<0.05) respectively in Nos+CMP compared to other groups. Also, expression of Bcl2, survivin, MMP-2 and MMP-9 was significantly downregulated in Nos+CMP treated cells (p<0.05). Further, investigations are currently being conducted to evaluate the synergistic anticancer effect of Nos and CMP in lung tumor xenografts in nude mice. Conclusion: Nos potentiated the anticancer activity of CMP in an additive to synergistic manner against lung cancer via cell cycle and apoptotic pathways. These findings suggest potential benefit for use of Nos+CMP in treatment of lung cancer. Citation Format: Ravi Doddapaneni, Ketan Patel, Mandip Singh. Synergistic anticancer effect of Noscapine and Camptothecin is mediated through apoptosis and cell cycle arrest in A549 lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2619. doi:10.1158/1538-7445.AM2015-2619

Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

BackgroundGlioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM in vitro and the role of midkine (MK) in this new combination treatment.MethodsMonolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM), Nos (10 μM) and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM) and ultrastructure (TEM) for 72 hrs. Results were statistically analyzed using the Student's t-test.ResultsThe combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72nd hr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely.ConclusionsThe combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.

Behavioral effect of naloxone on anxiolytic- like effect of noscapine in bulb/c mice

The effect of naloxone, a non-selective opioid antagonist on some anxiolytic and analgesic drugs is reported. Noscapine is an opioid alkaloid with antitussive effect that cannot be antagonized by naloxone. The anxiolytic-like effect of noscapine has been shown in light-dark model and elevated plus maze. In this study the effect of naloxone on anxiolytic effect of noscapine in light-dark model was investigated The measured parameters were time spent in light, time spent in dark, latency and number of tunnel transitions. Since locomotion could affect the behavioral pattern of the animals, locomotor activity was also measured. Our data show that naloxone alone has no effect on number of tunnel transition, latency, time spent in light and time spent in dark. However, naloxone could antagonize the anxiolytic-like effect of noscapine (1, 1.5 mg/kg) and decrease time spent in light area. The antagonistic effect of naloxone on anxiolytic-like effect of noscapine may be due to non-opioid receptors, involved in anxiety.

Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro

Peripheral neuropathy is a common, dose-limiting side effect of vincristine, a frontline therapy for acute lymphoblastic leukemia. Combination chemotherapy that reduces the neurotoxicity without compromising the efficacy of vincristine would improve patient outcomes. We performed in vitro studies using a combination of microtubule-binding antimitotics, noscapine and vincristine. In cell cultures containing neurons, astrocytes, and oligodendrocytes, vincristine caused demyelination as shown by transmission electron microscopy. A combination of vincristine and noscapine protected against demyelination. Human acute lymphoblastic and acute myelogenous leukemia cell lines CCRF-CEM and HL-60, respectively, were used to determine the antiproliferative effect of this novel drug combination. Vincristine and noscapine decreased cell proliferation with IC50 concentrations of 1 nM and 20 µM, respectively. Analysis of dose-effect relationships using isobolograms and combination indices demonstrated that noscapine acts synergistically with vincristine. Thus, noscapine is a promising candidate for use with vincristine to decrease neurotoxicity and enhance antineoplastic effectiveness.

The Use of Noscapine (Narcotine) as an Antitussive Agent

and similar compounds is based on a phenanthrene nucleus, whereas Noscapine is an isoquinoline derivative (related to papaverine). It is readily absorbed after oral or parenteral administration, disappears rapidly from the blood stream, and only traces appear in the urine. Its fate is unknown. It has been referred to as the least toxic of the opium alkaloids in mice, rats, and man. Up to 3 grams by mouth have been given to man with only minor side reactions. Chronic toxicity studies did not demonstrate any cumulative effects. No depressant action on respiration or the central nervous system has been observed up to toxic doses; stimulation may appear with higher doses. The effects of Noscapine on the gastrointestinal tract were insignificant. No effects on secretory activity and minimal effects on gastrointestinal movements were reported. Occasionally emesis and constipation were noted only with large doses. No significant analgesc action was observed. Potentiation of morphine analgesia with antagonism to side effects have been reported, but not definitely established. The parenteral use of Noscapine has been limited because of local pain. In experimental cough in animals and man, it was described as effective as codeine. No tolerance to the drug developed. Finally, although no antihistaminic action was found, it did inhibit the “allergic cough” in sensitized guinea pigs exposed to aerosols of specific antigen. It did not, however, prevent anaphylactic shock after injected antigen. In a study centering about the experimental production of cough in normal and asthmatic subjects, small doses of Narcotine (5 and 15 mg.) were demonstrated to have greater anti