THE EFFECTS OF LITHIUM CHLORIDE ACETAMINOPHEN AND VINORELBINE ON CYTOTOXICITY IN MDAH-2774 HUMAN OVARIUM TUMOR CELL LINE
Main Article Content
Abstract
In this study, the effects of vinorelbine (A microtubule inhibitor), para aminophenol derived acetaminophen and LiCl (a mood stabilizing agent) on monolayer and spheroid models of MDAH-2774 human ovarian cancer cell lines were investigated using both single and combined application of the drugs. The effects of the drugs on cell proliferation, cytotoxicity and S- phase fraction of cell cycle at 24,48 and 72 hours, respectively, were evaluated in cell culture. Evaluation of each drug in monolayer and spheroid cell culture compared to control group showed that vinorelbine, lithium and acetaminophen caused significant decrease in both cell proliferation and cell cycle progression and S-Phase of DNA synthesis. However, the effect of acetaminophen in relation to the other drugs was most pronounced.
There was no significant difference between drug combination groups and single drug groups in monolayer and spheroid cell culture. The data indicate that the effects of vinorelbine, lithium chloride and acetaminophen on monolayer and spheroid models of MDAH-2774 human ovarian cancer cell line caused a decrease in cell number in the cell cycle sythesis phase and prevented cell proliferation. We observed different size and shaps autophagic vacuols and defective mitochondria in the cytoplasm of the cells treated with vinorelbine. These findings were evaluated as a sign of autophagic cell death.
Keywords:
MDAH-2774, Acetaminophen, Lithium chloride, Vinorelbine, Cell culture, MDAH- 2774 Cell Line
Article Details
How to Cite
NURAY EREN, Selame et al.
THE EFFECTS OF LITHIUM CHLORIDE ACETAMINOPHEN AND VINORELBINE ON CYTOTOXICITY IN MDAH-2774 HUMAN OVARIUM TUMOR CELL LINE.
Medical Research Archives, [S.l.], v. 6, n. 11, nov. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1869>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v6i11.1869.
Section
Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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27. Hanley, ML., Elion, GB., Colvin, OM., Modrich, PL., Keir, S., Adams, DJ., Bigner, DD., Friedman, HS. Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors. Cancer Chemother Pharmacol. 1998; 42(6):479-82.
28. Sun, A., Shanmugam, I., Song, J., Terranova, PF., Li, B. Lithium suppresses cell proliferation by interrupting E2F-DNA interaction and subsequently reducing S-phase gene expression in prostate cancer. Prostate. 2007; 67(9): 976-988.
29. Kunnimalaiyaan, M., Vaccaro, AM., Ndiaye, MA., Chen, H. Inactivation of glycogen synthase kinase-3beta, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells. Mol Cancer Ther. 2007;6(3), 2007:1151-1158.
30. Posadas, I., Vellecco, V., Santos, P., Prieto-Lloret, J., Ceña, V. Acetaminophen potentiates staurosporine-induced death in a human neuroblastoma cell line. Br J Pharmacol. 2007; 150(5):577-585.
31. Crew, KD., Neugut, AI. Aspirin and NSAIDs: effects in breast and ovarian cancers. Curr Opin Obstet Gynecol. 2006;18(1): 71-75.
32. Altinoz, MA., Korkmaz, R. NF-kappaB macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma. 2004;51(4):239-247.
2. Bilir, A., Altinoz, MA., Attar, E., Erkan, M., Aydiner, A. Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro. Neoplasma. 2002;49 (1):38-42.
3. Freedman, RS., Phil, E., Kusyk, C., Gallager, HS., Rutledge, F. Chracterization of an ovarian carcinoma cell line. Cancer 1978¸42: 2353-2359.
4. Gregory, RK., Smith, IE.Vinorelbine--a clinical review. Br J Cancer 2000;82(12):1907-1913
5. Gilloteaux J, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774)cells following vitamin C, vitamin K3 or vitamin C:K3 treatment. Microsc Microanal.2003; 9(4): 311-29.
6. Gregory, RK and Smith, IE. Vinorelbine - a Clinical Review, British Journal of Cancer. 2000 ; 82(12): 1907-1913.
7. Gidding, CEM., Kellie, SJ., Kamps, WA., Graaf, SSN. Vincristine revisited. Critical Reviews in Oncology Hematology. 1999. 29(3): 267-287.
8. El Hafny, B., Cano, N., Piciotti, M., Regina, A., Schemnann, JM., Roux, F. Role of P-glycoprotein in Colchicine and Vinblastine Cellular Kinetics in an İmmortalized Rat Brain Microvessel Endothelial Cell Line. Biochemical Pharmacology. 1997; 53(11):1735-1742.
9. Cragg,GM., Newman, DJ. Plants as a Source of Anti-cancer Agents. Journal of Ethnopharmacology, 2005; 100(1-2) : 72-79.
10. Mitchell, JA., Warner, TD., Cyclo-oxygenase-2: Pharmacology, Physio-logy, Biochemistry and Relevance to NSAID Therapy. British Journal of Pharmacology. 1999; 128 :1121-1132.
11. Oksuz, E., Atalar, F., Tanırverdi, G., Bili, A., Shahzadi, A., Yazici, Z. Therapeutic potential of cyclooxy-genase-3 inhibitors in the mana-gement of glioblastoma. J Neuro-oncol. 2016; 126(2): 271-8.
12. Tseng, WW., Deganutti, A., Chen, MN., Saxton, RE., Liu, CD. Selective Cyclooxygenase-2 İnhibitor Rofecoxib (Vioxx) İnduces Expression of Cell Cycle Arrest Genes and Slows Tumor Growth in Human Pancreatic Cancer. Journal of Gastrointestinal Surgery. 2002;6(6): 838-843.
13. Burford, CR., Barnes, MN., Oel-schlager, DK., Myers, RB., Talley, TI., Partridge. EE., Grizzle, WE. Effects of Nonsteroidal Anti-Inflamamatory Agents (NSAIDs) on Ovarian Carcinoma Cell Lines: Preclinical Evaluation of NSAIDs as Chemopreventive Agents.Clinical Cancer Research. 2002; 8: 202-209.
14. Zhao, X., Xu, Z., Li, H., NSAIDs Use and Reduced Metastasis in Cancer Patients:results from a meta-analysis. Sci Rep. 2017;7(1):1875.
15. Genç, S., Attar,E., Gürdöl,F., Kendigelen,S., Bilir,A., Serdaroğlu, H. The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture. Clin Exp Med. 2007; 1:6-10.
16. Gurpinar, E., Grizzle, WE., Piazza GA. NSAIDs inhibit tumorigenesis, but how? Clin Cancer Res. 2014; 20(5):1104-13.
17. Erguven, M., Oktem, G., Kara, AN., Bili,r A. Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels. Oncol Lett. 2016; 12(4): 2948-2955.
18. Sabancι, PA., Ergüven, M,, Yazιhan, N., Aktaş, E., Aras, Y., Civelek, E., Aydoseli, A., Imer,M., Gürtekin, M., Bilir, A. Sorafenib and lithium chloride combination treatment shows promising synergistic effects in human glioblastoma multiforme cells in vitro but midkine is not implicated. Neurol Res. 2014 Mar;36(3):189 97.
19. Lin,CF., Chen,CL., Chiang,CW., Jan,MS., Huang, WC., Lin,YS. GSK-3beta Acts Downstream of PP2A and the PI 3-kinase-Akt Pathway, and Upstream of Caspase-2 in Ceramide İnduced Mitochondrial Apoptosis. Journal of Cell Science.2007; 120(16):2935-2943.
20. Zaragosi, LE.,Wdziekonski,B., Fontaine, C., Villageois, P., Peraldi,P., Dani, C. Effects of GSK3 İnhibitors on İn Vitro Expansion and Differentiation of Human Adipose-Derived Stem Cells into Adipocytes. BMC Cell Biology. 2008; 13: 9-11.
21. Gunin, AG., Emelianov, VU., Mironkin, IU., Morozov, MP., Tolmachev, AS. Lithium Treatment Enhances Estradiol-induced Proli-feration and Hyperplasia Formation in the Uterus of Mice. European Journal of Obstetrics Gynecology and Reproductive Biology.2004; 114(1): 83-91.
22. Mao, CD., Hoang, P,. DiCorleto, PE. Lithium İnhibits Cell Cycle Progress-ion and İnduces Stabilization of p53 in Bovine Aortic Endothelial Cells,'' Journal of Biological Chemistry. 2001; 276(28): 26180-26188.
23. Cao, Q., Lu, X., Feng, YJ. Glycogen Synthase Kinase-3β Positively Regulates the Proliferation of Human Ovarian Cancer Cells. Cell Research .2006; 6: 671-677.
24. Askar, N., Cirpan, T., Toprak, E., Karabulut, B., Selvi, N., Terek, MC., Uslu, R., Sanli, UA., Goker E. Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity. Int J Gynecol Cancer. 2006;16(4):1552-6.
25. Cramer, DW., Harlow, BL., Titus-Ernstoff, L., Bohlke, K., Welch, WR., Greenberg, ER.Over-the-counter analgesics and risk of ovarian cancer. Lancet. 1998; 351(9096): 104-7.
26. Hayakawa, A., Kawamoto, Y., Nakajima, H., Sakai, J., Takasawa, R., Nakashima, I. Bid truncation mediated by caspases-3 and -9 in vinoralbine-induced apoptosis. Apoptosis .2008; 13(4): 523-530.
27. Hanley, ML., Elion, GB., Colvin, OM., Modrich, PL., Keir, S., Adams, DJ., Bigner, DD., Friedman, HS. Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors. Cancer Chemother Pharmacol. 1998; 42(6):479-82.
28. Sun, A., Shanmugam, I., Song, J., Terranova, PF., Li, B. Lithium suppresses cell proliferation by interrupting E2F-DNA interaction and subsequently reducing S-phase gene expression in prostate cancer. Prostate. 2007; 67(9): 976-988.
29. Kunnimalaiyaan, M., Vaccaro, AM., Ndiaye, MA., Chen, H. Inactivation of glycogen synthase kinase-3beta, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells. Mol Cancer Ther. 2007;6(3), 2007:1151-1158.
30. Posadas, I., Vellecco, V., Santos, P., Prieto-Lloret, J., Ceña, V. Acetaminophen potentiates staurosporine-induced death in a human neuroblastoma cell line. Br J Pharmacol. 2007; 150(5):577-585.
31. Crew, KD., Neugut, AI. Aspirin and NSAIDs: effects in breast and ovarian cancers. Curr Opin Obstet Gynecol. 2006;18(1): 71-75.
32. Altinoz, MA., Korkmaz, R. NF-kappaB macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma. 2004;51(4):239-247.