BIOMAT Database Logo BIOMAT Database Logo

Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line. 2006

G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Department of Histology and Embryology, Ege University School of Medicine, TR-35100 Izmir, Turkey. goktem@med.ege.edu.tr

Multicellular tumor spheroids (MTS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on MTS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the "liquid overlay" technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2'-deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis.

UI MeSH Term Description Entries
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077143 Docetaxel A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER. Docetaxel Anhydrous,Docetaxel Hydrate,Docetaxel Trihydrate,Docetaxol,N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol,NSC 628503,RP 56976,RP-56976,Taxoltere Metro,Taxotere,N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol,RP56976
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D000972 Antineoplastic Agents, Phytogenic Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
D043823 Taxoids A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS. Taxanes,Taxoid
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D048708 Cell Growth Processes Processes required for CELL ENLARGEMENT and CELL PROLIFERATION. Processes, Cell Growth

Related Publications

G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression in fulminant hepatic failure.
November 2002, Journal of hepatology,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
The effects of Gemcitabine and Vinorelbine on inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) distribution of MCF-7 breast cancer cells.
January 2011, Acta histochemica,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents.
September 2002, Journal of endocrinological investigation,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice.
September 2001, Acta physiologica Scandinavica,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Is the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthases an early event in breast carcinogenesis?
January 2010, The breast journal,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival.
April 2001, British journal of pharmacology,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Mitochondrial nitric oxide synthase is not eNOS, nNOS or iNOS.
November 2003, Free radical biology & medicine,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Recombinant arginine deiminase as a differential modulator of inducible (iNOS) and endothelial (eNOS) nitric oxide synthetase activity in cultured endothelial cells.
November 2003, Biochemical pharmacology,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Inducible nitric oxide synthase (iNOS): role in asthma pathogenesis.
October 2007, Indian journal of biochemistry & biophysics,
G Oktem, and A Bilir, and N Selvi, and M E Yurtseven, and S Vatansever, and U Ates, and A Uysal, and S B Omay
Inducible nitric oxide synthase (iNOS) in sinonasal polyp pathogenesis.
January 2013, B-ENT,
Copied contents to your clipboard!