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Background and Objective: For most of cancers there is no treatment and most of them ended in death. So, the first investigational stage is evaluation of toxic effects of drug fractions on cancer cells. Artemisia species are important medicinal plants throughout the world. In this study, anti-tumoral effects of seven Artemisia spp. fractions from Iran were studied on cancer and normal cells. Material and Methods: Ethanol, ethylacetate, dichloromethane and hexane fractions of seven Artemisia species from Iran were prepared by step to step procedure. Cultivated cancer and fibroblast cells were incubated with different concentrations of fractions for 72 hours and cytotoxicity was determined using MTT assay. Results were reported as IC50 (concentration that kills 50 percent of cells). Results: Obtained results showed strong and dose-dependent inhibition of cancer cell growth by different Artemisia fractions. The most cytotoxicity effects were for dichloromethane fraction from Artemisia biennis on cervix cancer cells, dichloromethane fraction from Artemisia ciniformis on gastric cancer cells and dichloromethane fraction from Artemisia diffusa on colon cancer cells. Ethylacetate, dichloromethane and hexane fractions from Artemisia biennis, hexane fraction from Artemisia ciniformis, hexane fraction from Artemisia santulina and ethylacetate fraction from Artemisia vulgaris had the least toxic effect on normal L929 cells. Conclusion: Some isolated fractions caused a significant decrease in cancer cell growth and had less toxicity on normal cells. So, study on Artemisia in prevention or efficient treatment of different cancers is useful. Study the effect of effective fractions on apoptosis induction and determination of their mechanisms of actions is suggested.

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Background and Objective: Compounds of heavy metals such as vanadium, nickel, and cobalt can be useful in treatment of many diseases. There are several reports on the biological effects of vanadium compounds including insulin-like action and reduction of hypertension. A number of studies on vanadium have shown its promising ability to inhibit cancers in a variety of malignant cell lines. The goal of this study was to examine the anti-proliferative and apoptosis-inducing characteristics of some newly synthesized shifft-based vanadium (VOLComplex:C19H20N2O5V) on K562 leukemia cells. Materials and Methods: The MTT results show that the K562 cells viability is sensitive to the Vol complex in a concentration dependent manner. It was evident that the VOL complexe, up to a dose of 350 µg/ml, were non-cytotoxic in vitro after 48 hours of incubation time. In order to investigate if the Vol complexe have just anticancer effect, we designed further studies with non-cytotoxic doses of the complex. Based on the cell viability data, the concentrations of 150, 250, and 350 µg/ml of the VOL complexe were selected to treat the K562 cells for 12, 24, and 48 hr to induce apoptosis. Results: The results of apoptosis analysis and flow cytometric examination show that exposure of the K562 cells to non-cytotoxic dosses of the VOL complex leads to induction of apoptosis in a dose- and time-dependent manner. The highest level of apoptosis (37.96%) occurred after 48 hr of treatment in response to 350 µg/ml of the Vol complex. Moreover, the cell cycle analysis shows that the VOL complex induces a G0/G1 arrest. Conclusion: Our findings indicate that the Vol complex, even at a non-cytotoxic dose, has an apoptosis inducing effect, and that it is capable of arresting the affected cells in the G0/G1 phase of the cell cycle. Taken together, based on their role on induction of apoptosis and cell cycle arrest, VOL complexes may have the potential for being included in an anti-cancer drug discovery program in the near future.

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Background and Objective: Photodynamic therapy is a treatment that uses photosensitizer and intense visible light. When photosensitizers get exposed to a specific light wavelength (preferentially in the red region), they produce reactive oxygen species that are toxic to cells. Recently, attention has been focused on porphyrins and their analogs as photosensitizers. Zn (II) tetrapyridinoporphyrazin complex is a water-soluble photosensitizer that has a good potential for application in photodynamic therapy. In this study, phototoxic effect of this complex on HeLa cancer cell line has been investigated. Materials and Methods: HeLa cell cultures were treated with different concentrations of Zn (II) tetrapyridinoporphyrazin. The cytotoxic effects were measured both in the presence and absence of light using the MTT assay. The light source was a 150W tungsten halogen lamp equipped with a red filter. Results: Our data indicate that porphyrazine’s photocytotoxicity is remarkably more significant than its cytotoxycity in the dark. Statistical analysis showed the effective dose (ED50) values in the dark and light conditions were 8.6 and 4.2 µM, respectively. In addition, the results imply that in the range of 0-12 µM, the increase in the complex concentration correlates with the increase in the cytotoxicity effect. However, the cytotoxicity decreases at the higher concentration (50µM), which is likely due to aggregation of the complex. Conclusion: Our results show that Zn (II) tetrapyridinoporphyrazin complex may be a promising photosensitizer for innovative photodynamic therapy and may have a high potential application in cancer treatment. Furthermore, it seems to have more benefits compared to other known photosensitizers.

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Background and Objective: Due to progressive increase in the number of cases of cancer, there is a need to develop anti- tumor compounds. Statins have a variety of different effects on proliferation, migration and survival of cells and have been suggested as proper candidates for the inhibition of this disease. The aim of this study was to determine cytotoxicity effects of Atorvastatin with variety of concentrations on the growth of MCF7 cell line. Materials and Methods: MCF7 cell lines were incubated in RPMI 1640 medium supplemented with 10% FBS in a humidified incubator (37 ºC & 5% CO2). Different concentrations of Atorvastatin on quantitative proliferation of the cell line were determined by Dimethyl Thiazol Tetrazolium bromide (MTT) colorimetric assay and Trypan blue. The data were analyzed by SPSS version 11.5. The statistical analysis was performed by one-way ANOVA and Tukey's tests. Results: There was no statistical significance in cytotoxicity effect of 1 µmol and 0.1 µmol of Atorvastatin on survival of MCF7 cells after 24, 48 and 72 hrs comparing to control cells. But in 10 µmol concentration of Atorvastatin, a significant decrease was observed in survival of MCF7 cells at the mentioned time points. Conclusion: Different concentrations of Atorvastatin have different effects on the growth of cultured cell lines. It seems that 10µmol concentration decreases growth of cultured human breast cancer cells. Further animal studies on this subject are suggested.

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Background and Objective: Currently, as an important trace element, is increasingly used in drug delivery, hyperthermia and diagnosis and treatment of cancer. The main objective of this study was to determine the cytotoxicity effects of nanostructure iron oxide and to implement the findings for its safe applications. Materials and Methods: Urea coated iron oxide nanorods were modified with fetal bovine serum. Toxicity at doses of 100 and 400μg/ml in modified nanorods vs. non-modified nanorods was tested via (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Toxicity of Polyethylene glycol (PEG) coated iron oxide nanorods with identical doses were compared with Urea coated iron oxide nanorods by MTT assay. All the procedures were carried out on L929 cell lines for periods of 24 and 48 h. Results: Cells on exposure to modified nanorods had more viability than non-modified ones at all doses and all the time points. PEG coated in comparison to urea coated nanorods exhibiteda higher cell death at all doses and all time points. Conclusion: Based on the obtained results, unmodified nanorods in comparison to modified ones demonstrated more toxicity which appears to stem from formation of a protein ring called Hard Corona around these nanorods in a protein contained media. Protein rings are not formed in the modified nanorods. Meanwhile, the reduction of apoptosis in urea coated nanorods as compared with PEG, verifies that the type of coating depending on size is effective on cellular toxicity.

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Background and Objective: Pomalidomide - a combination of Lenalidomide and Thalidomide drugs- is one of the newest anticancer drugs. Pomalidomide induces apoptosis in cancer cells. Furthermore, few studies indicating its relatively low cytotoxic effects on normal peripheral blood cells have been carried out. However, there is yet no information about the effects of Pomalidomide on bone marrow cells that contain important immune cells. In this study, the effect of Pomalidomide on normal bone marrow mononuclear cells was studied. Materials and Methods: The samples obtained from individuals who clinically needed bone marrow examination, but finally were diagnosed with no serious pathologic conditions in their leukocytes. Remained bone marrow aspirates were obtained and mononuclear cells were isolated. Half of the mononuclear cells were cultured with Pomalidomide (final concentration 10μM) and the remaining half (control group) were cultured with media alone. After 48h incubation, vital activity (MTT) and cell apoptosis induction rates were assessed. Results: The results showed that the vital activity of bone marrow mononuclear cells cultured in the presence of Pomalidomide increased significantly compared to the control group (P<0.05). However, Pomalidomide had no apoptosis induction and the rate of apoptotic cells had no significant difference with control group. Conclusion: Pomalidomide moderately stimulates the viability (or activity) of normal bone marrow mononuclear cells to improve and maintain them. Also, unlike most anticancer drugs it has no observable toxic effect or apoptosis induction on these cells. So, it may be concluded that Pomalidomide may be more favorable in preventing the side effects of anticancer drugs on normal cells. References 1- Melchert M, List A. The thalidomide saga. Int J Biochem Cell Biol. 2007 39(7): 1489-99. 2- Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010 24(1): 22-32. 3- Shalapour S, Zelmer A, Pfau M, et al. The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells invitro and invivo. Clin Cancer Res. 2006 12(18): 5526-32. 4- Baskić D, Popović S, Ristić P, Arsenijević NN. Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol Int. 2006 30(11): 924-32. 5- Lacy MQ. New immunomodulatory drugs in myeloma. Curr Hematol Malig Rep. 2011 6(2): 120-5. 6- Sedlarikova L, Kubiczkova L, Sevcikova S, Hajek R. Mechanism of immunomodulatory drugs in multiple myeloma. Leuk Res. 2012 36(10): 1218-24. 7- Gorgun G, Calabrese E, Soydan E, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010 116(17): 3227-37. 8- Schey S, Ramasamy K. Pomalidomide therapy for myeloma. Expert Opin Investig Drugs. 2011 20(5): 691-700. 9- Schafer PH, Gandhi AK, Loveland MA, et al. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 305(3): 1222-32. 10- Marriott J, Clarke I, Dredge K, Muller G, Stirling D, Dalgleish A. Thalidomide and its analogues have distinct and opposing effects on TNF- α and TNFR2 during co-stimulation of both CD4+ and CD8+ T cells. Clin & Exp Immunol. 2002 130(1): 75-84. 11- Lacy MQ, Tefferi A. Pomalidomide therapy for multiple myeloma and myelofibrosis: an update. Leuk Lymphoma. 2011 52(4): 560-6. 12- Ahmadbeigi N, Soleimani M, Mortazavi Y. The efficiency of density gradient for separation of mesenchymal stem cells from bone marrow sample. Zanjan Unv Med Sci J. 2011 19 (77): 62-69. 13- Hernández P, Cortina L, Artaza H, et al. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: A comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis. 2007 194(2): e52-e6. 14- Hay FC, Westwood OM. Practical immunology 4th edition. UK: Wiley 2008. 15- Lacy MQ, McCurdy AR. Pomalidomide. Blood. 2013 122(14): 2305-9. 16- Chanan-Khan A, Swaika A, Paulus A, et al. Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma. Blood Cancer J. 2013 3(9): e143. 17- Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004 4(4): 314-22. 18- Kim JH, Scialli AR. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol Sci. 2011 122(1): 1-6. 19- Nicholas A, Boon MA, Nicki R, Brian R, Walker JA, Hunter D. Principle And practice of medicine. 20th Edition. UK: Churchill Livingstone 2006. 20- Liu W, Henry J, Meyer B, Bartlett J, Dalgleish A, Galustian C. Inhibition of metastatic potential in colorectal carcinoma invivo and invitro using immunomodulatory drugs (IMiDs). Br J Cancer. 2009 101(5): 803-12. 21- Moutouh-de Parseval LA, Verhelle D, Glezer E, et al. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest. 2008 118(1): 248-58. 22- Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009 27: 4563-9.