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Apoptotic effects of some carbazole derivatives on lung carcinoma and glioma cell lines

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Abstract

In this study, we aimed to study the apoptotic effects of 2-[(9-ethyl-9H-carbazol-3-yl)amino]-2-oxoethyl N,N-disubstituted dithiocarbamates on A549 lung carcinoma and C6 glioma cell lines. Cytotoxicity analyses of DNA synthesis and detection of apoptosis by flow cytometry were evaluated to determine the anticancer activity of the compounds on both cell lines. Compounds 2, 5, and 7 which exhibited significant cytotoxic activity in MTT assay were chosen for flow cytometric analyses to determine the apoptotic percent of cells. These compounds also exhibited better DNA synthesis inhibition activity on cancer cells. Finally, acetylcholinesterase inhibition potentials of the compounds were measured. Compound 7 carrying 4-(2-dimethylaminoethyl)piperazin-1-yl moiety was the most active apoptotic agent against A549 and C6 cells. Apoptotic effect of this compound can be attributed to its AchE inhibition activity. Compounds 2 and 5 also showed apoptotic effects on C6 glioma cell lines. Compounds 2, 5, and 7 can be identified as the most promising anticancer agents against A549 and C6 cancer cell lines.

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References

  • Akué-Gédu R, Letribot B, Saugues E, Debiton E, Anizon F, Moreau P (2012) Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives. Bioorg Med Chem Lett 22(11):3807–3809

    Article  PubMed  Google Scholar 

  • Arima N, Arimura K, Tokito Y, Sakaki Y, Matsushita K, Orihara K, Akimoto M, Ozaki A, Kukita T, Hagiwara T, Hamada H, Tei C (2004) HTLV-I Tax protein inhibits apoptosis induction but not G1 arrest by pyrrolidinedithiocarbamate, an anti-oxidant, in adult T cell leukemia cells. Exp Hematol 32:195–201

    Article  PubMed  CAS  Google Scholar 

  • Asche C, Demeunynck M (2007) Antitumor carbazoles. Anticancer Agents Med Chem 7(2):247–267

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Peng F, Cui QC, Daniel KG, Orlu S, Liu J, Dou QP (2005) Inhibition of prostate cancer cellular proteasome activity by a pyrrolidine dithiocarbamate-copper complex is associated with suppression of proliferation and induction of apoptosis. Front Biosci 10:2932–2939

    Article  PubMed  CAS  Google Scholar 

  • Conscience JF, Meier W (1980) Coordinate expression of erythroid marker enzymes during dimethyl-sulfoxide induced differentiation of friend erythro-leukemia cells. Exp Cell Res 125(1):111–119

    Article  PubMed  CAS  Google Scholar 

  • Dodds HM, Hanrhan J, Rivory LR (2001) The inhibition of acetylcholinesterase by irinotecan and related camptothecins: key structural properties and experimental variables. Anticancer Drug Des 16(4–5):239–246

    PubMed  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  • Fukuda M, Oka M, Soda H, Kinoshita A, Fukuda M, Nagashima S, Kuba M, Takatani H, Tsurutani J, Nakamura Y, Kasai T, Inoue Y, Soejima Y, Kohno S (2004) Phase II study of irinotecan combined with carboplatin in previously untreated non-small-cell lung cancer. Cancer Chemother Pharmacol 54(6):573–577

    Article  PubMed  CAS  Google Scholar 

  • Gearhart JD, Mintz B (1974) Contact-mediated myogenesis and increased acetylcholinesterase activity in primary cultures of mouse terato-carcinoma cells. Proceedings of the National Academy of Science USA 71(4):1734–1738

  • Hajnoczky G, Csordas G, Krishnamurthy R, Szalai G (2000) Mitochondrial calcium signalling driven by the IP3 receptor. J Bioenerg Biomembr 32(1):15–25

    Article  PubMed  CAS  Google Scholar 

  • Karaburun AC, Kaplancikli ZA, Gundogdu-Karaburun N, Demirci F (2011) Synthesis, antibacterial and antifungal activities of some carbazole dithiocarbamate derivatives. Lett Drug Des Discov 8:811–815

    Article  CAS  Google Scholar 

  • Koronkiewicz M, Chilmonczyk Z, Kazimierczuk Z (2012) Proapoptotic effects of novel pentabromobenzylisothioureas in human leukemia cell line. Med Chem Res 21(10):3111–3118

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Yu YY, Zhu ZG, Ji YB, Zhang Y, Liu BY, Chen XH, Lin YZ (2005) Effect of NF-kappaB constitutive activation on proliferation and apoptosis of gastric cancer cell lines. Eur Surg Res 37:105–110

    Article  PubMed  CAS  Google Scholar 

  • Malaguarnera L, Pilastro MR, DiMarco R, Scifo C, Renis M, Mazzarino MC, Messina A (2003) Cell death in human acute myelogenous leukemic cells induced by pyrrolidinedithiocarbamate. Apoptosis 8:539–545

    Article  PubMed  CAS  Google Scholar 

  • Malikova J, Swaczynova J, Kolar Z, Strnad M (2008) Anticancer and antiproliferative activity of natural brassinosteroids. Phytochemistry 69(2):418–426

    Article  PubMed  CAS  Google Scholar 

  • Massoulié J (2002) The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11:130–143

    Article  PubMed  Google Scholar 

  • Massoulié J, Bon S (1982) The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Annu Rev Neurosci 5:57–106

    Article  PubMed  Google Scholar 

  • Meli M, D’Alessandro N, Tolomeo M, Rausa L, Notarbartolo M, Dusonchet L (2003) NF-kappaB inhibition restores sensitivity to Fas-mediated apoptosis in lymphoma cell lines. Ann N Y Acad Sci 1010:232–236

    Article  PubMed  CAS  Google Scholar 

  • Morais C, Pat B, Gobe G, Johnson DW, Healy H (2006) Pyrrolidine dithiocarbamate exerts anti-proliferative and pro-apoptotic effects in renal cell carcinoma cell lines. Nephrol Dial Transplant 21(12):3377–3388

    Article  PubMed  CAS  Google Scholar 

  • Mossmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  Google Scholar 

  • Nie L, Wise ML, Peterson DM, Meydani M (2006) Avenanthramide, a polyphenol from oats, inhibits vascular smooth muscle cell proliferation and enhances nitric oxide production. Atherosclerosis 186(2):260–266

    Article  PubMed  CAS  Google Scholar 

  • Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S (2011) Analysis of anticancer drugs: a review. Talanta 85:2265–2289

    Article  PubMed  CAS  Google Scholar 

  • Onganer PU, Djamgoz MB, Whyte K, Greenfield SA (2006) An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line. Biochim Biophys Acta 1760(3):415–420

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Espejo F, Cabezas-Herrera J, Illana J, Campoy FJ, Vidal CJ (2002) Cholinesterase activity and acetylcholinesterase glycosylation are altered in human breast cancer. Breast Cancer Res Treat 72:11–22

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Espejo F, Cabezas-Herrera J, Illana J, Campoy FJ, Munoz- Delgado E, Vidal CJ (2003) Breast cancer metastasis alters acetylcholinesterase activity and the composition of enzyme forms in axillary lymph nodes. Breast Cancer Res Treat 80:105–114

    Article  PubMed  CAS  Google Scholar 

  • Saez-Valero J, Vidal CJ (1996) Biochemical properties of acetyl- and butyrylcholinesterase in human meningioma. Biochim Biophys Acta 1317:210–218

    Article  PubMed  CAS  Google Scholar 

  • Saez-Valero J, Poza-Cisneros G, Vidal CJ (1996) Molecular forms of acetyland butyrylcholinesterase in human glioma. Neurosci Lett 206:173–176

    Article  PubMed  CAS  Google Scholar 

  • Sberna G, Saez-Valero J, Beyreuther K, Masters CL, Small DH (1997) The amyloid beta-protein of Alzheimer’s disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. J Neurochem 69:1177–1184

    Article  PubMed  CAS  Google Scholar 

  • Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA (1992) Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med 175:1181–1194

    Article  PubMed  CAS  Google Scholar 

  • Shaharyar M, Abdullah MM, Bakht MA, Majeed J (2010) Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur J Med Chem 45:114–119

    Article  PubMed  CAS  Google Scholar 

  • Silverman RB (2004) The organic chemistry of drug design and drug action. Elsevier Academic Press USA, Burlington, pp 298–302

    Google Scholar 

  • Thunnissen FB (2009) Acetylcholine receptor pathway and lung cancer. J Thorac Oncol 4(8):943–946

    Article  PubMed  Google Scholar 

  • Varache-Lembège M, Moreau S, Larrouture S, Montaudon D, Robert J, Nuhrich A (2008) Synthesis and antiproliferative activity of aryl- and heteroaryl-hydrazones derived from xanthone carbaldehydes. Eur J Med Chem 43(6):1336–1343

    Article  PubMed  Google Scholar 

  • Xia HJ, Yang G (2005) Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations. Cell Res 15(2):83–91

    Article  PubMed  CAS  Google Scholar 

  • Zhang XJ, Yang L, Zhao Q, Caen JP, He HY, Jin QH, Guo LH, Alemany M, Zhang LY, Shi YF (2002) Induction of acethylcholinesterase expression during apoptosis in various cell types. Cell Death Differ 9:790–800

    Article  PubMed  CAS  Google Scholar 

  • Zovko A, Sepcic K, Turk T, Faimali M, Garaventa F, Chelossi E, Paleari L, Falugi C, Aluigi MG, Angelini C, Trombino S, Gallus L, Ferrando S (2009) New aspects of the relationship between acethylcholinesterase activity and cancer I: Poly-Aps experiments. Wseas Transact biol biomed 6(3):58–69

    CAS  Google Scholar 

Download references

Acknowledgments

We gratefully thank to the Medicinal Plants, Drugs and Scientific Research Center (BIBAM), Anadolu University, where the cell culture studies and flow cytometry analyses of the present work were carried out in.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Gülşen Akalın Çiftçi & Halide Edip Temel

  2. Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Şafak Ulusoylar Yıldırım

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey

    Zafer Asım Kaplancıklı & Mehlika Dilek Altıntop

  4. Medicinal Plants, Drugs and Scientific Research Center (AUBIBAM), Anadolu University, Eskişehir, Turkey

    Lütfi Genç

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  1. Gülşen Akalın Çiftçi
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Correspondence to Halide Edip Temel.

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Çiftçi, G.A., Temel, H.E., Yıldırım, Ş.U. et al. Apoptotic effects of some carbazole derivatives on lung carcinoma and glioma cell lines. Med Chem Res 22, 3751–3759 (2013). https://doi.org/10.1007/s00044-012-0325-2

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  • DOI: https://doi.org/10.1007/s00044-012-0325-2

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