Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Research Article

ROS-mediated Genotoxicity and Apoptosis Induced by a Novel Salicylaldimine Derivatives in Human Cervical Cancer Cells

Author(s): Yasin Tülüce*, Halgurd Nadhim Mohammed, İsmail Koyuncu, Ahmet Kiliç and Mustafa Durgun

Volume 30, Issue 33, 2023

Published on: 27 December, 2022

Page: [3815 - 3829] Pages: 15

DOI: 10.2174/0929867330666221026162452

Price: $65

conference banner
Abstract

Background: Cervical cancer is one of the most common types of cancer among women. Therefore, cancer studies are underway for a new chemo-agent with more effect on cancer cells and fewer side effects on normal human healthy cells. The currently studied novel ligand L2b as a reduced salicylaldimine derivative was examined in seven cell lines, HeLa, DU-145, PC3, DLD-1, ECC, HT-29, and PNT1-A as a control.

Aim: Because of the antiproliferative ability of L2b, this study intends to look at the apoptotic, cytotoxic, and genotoxic activity of L2b on HeLa.

Methods: For this purpose, MTT assay is for screening cytotoxic effects, comet assay for looking for DNA damaging or genotoxicity levels, ELISA and DNA fragmentation for apoptotic measuring, AO/EB stain test for checking the rates of live, apoptotic and necrotic cells were performed. To reveal the oxidative state, OSI was assessed by total oxidant and antioxidant status ratios. FRAP assay was calculated for ferric-reducing antioxidant power, using total thiol and GSH assays to measure the antioxidant values of HeLa cells.

Results: Of this result, we have found a tremendous effect of L2b on HeLa cells, especially in raising the ROS rate, damaging their DNA, and causing a range of reactions leading to apoptosis.

Conclusion: In conclusion, the data predict which ligand L2b is capable of rising apoptosis in vitro cervical cancer cell line studied. Further cancer studies are needed to reveal the apoptosis pathways of the ligand L2b in the HeLa cell line and its anticancer drug potency in vivo work.

« Previous
[1]
Baken, L.A.; Koutsky, L.A.; Kuypers, J.; Kosorok, M.R.; Lee, S.K.; Kiviat, N.B.; Holmes, K.K. Genital human papillomavirus infection among male and female sex partners: Prevalence and type-specific concordance. J. Infect. Dis., 1995, 171(2), 429-432.
[http://dx.doi.org/10.1093/infdis/171.2.429] [PMID: 7844382]
[2]
Gökçe, Ö.; Yılmaz, A.; Gürbüz, V.; Konaç, E.; Ekmekçi, A. Apoptotic effect of vinorelbine on human cervical cancer HeLa cells. J. Dev. Med, 2011, 25, 5-14.
[3]
Waggoner, S.E.; Darcy, K.M.; Tian, C.; Lanciano, R. Smoking behavior in women with locally advanced cervical carcinoma: A Gynecologic Oncology Group study. Am. J. Obstet. Gynecol., 2010, 202(3), 283.e1.
[http://dx.doi.org/10.1016/j.ajog.2009.10.884] [PMID: 20044066]
[4]
Loft, A.; Berthelsen, A.K.; Roed, H.; Ottosen, C.; Lundvall, L.; Knudsen, J.; Nedergaard, L.; Højgaard, L.; Engelholm, S.A. The diagnostic value of PET/CT scanning in patients with cervical cancer: A prospective study. Gynecol. Oncol., 2007, 106(1), 29-34.
[http://dx.doi.org/10.1016/j.ygyno.2007.03.027] [PMID: 17482666]
[5]
Huang, H.C.; Chang, J.H.; Tung, S.F.; Wu, R.T.; Foegh, M.L.; Chu, S.H. Immunosuppressive effect of emodin, a free radical generator. Eur. J. Pharmacol., 1992, 211(3), 359-364.
[http://dx.doi.org/10.1016/0014-2999(92)90393-I] [PMID: 1535596]
[6]
Koivusalo, R.; Hietanen, S. The cytotoxicity of chemotherapy drugs varies in cervical cancer cells depending on the p53 status. Cancer Biol. Ther., 2004, 3(11), 1177-1183.
[http://dx.doi.org/10.4161/cbt.3.11.1340] [PMID: 15640620]
[7]
Fujimoto, J. Novel strategy of anti-angiogenic therapy for uterine cervical carcinomas. Anticancer Res., 2009, 29(7), 2665-2669.
[PMID: 19596943]
[8]
Tülüce, Y.; Lak, P.T.A.; Koyuncu, İ.; Kılıç, A.; Durgun, M.; Özkol, H. The apoptotic, cytotoxic and genotoxic effect of novel binuclear boron-fluoride complex on endometrial cancer. Biometals, 2017, 30(6), 933-944.
[http://dx.doi.org/10.1007/s10534-017-0060-8] [PMID: 29052084]
[9]
Tülüce, Y.; Ahmed, B.A.; Koyuncu, İ.; Durgun, M. The cytotoxic, apoptotic and oxidative effects of carbonic anhydrase IX inhibitor on colorectal cancer cells. J. Bioenerg. Biomembr., 2018, 50(2), 107-116.
[http://dx.doi.org/10.1007/s10863-018-9749-9] [PMID: 29520697]
[10]
Perez, R.P. Cellular and molecular determinants of cisplatin resistance. Eur. J. Cancer, 1998, 34(10), 1535-1542.
[http://dx.doi.org/10.1016/S0959-8049(98)00227-5] [PMID: 9893624]
[11]
Wang, X.D.; Gu, L.Q.; Wu, J.Y. Apoptosis-inducing activity of new pyrazole emodin derivatives in human hepatocellular carcinoma HepG2 cells. Biol. Pharm. Bull., 2007, 30(6), 1113-1116.
[http://dx.doi.org/10.1248/bpb.30.1113] [PMID: 17541163]
[12]
Kilic, A.; Ozbahceci, O.; Durgun, M.; Aydemir, M. Different hemi-salen/salan ligand containing binuclear boron-fluoride complexes: Synthesis, spectroscopy, fluorescence properties, and catalysis. Polycycl. Aromat. Compd., 2019, 39(3), 248-265.
[http://dx.doi.org/10.1080/10406638.2017.1314973]
[13]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[14]
Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res., 1988, 175(1), 184-191.
[http://dx.doi.org/10.1016/0014-4827(88)90265-0] [PMID: 3345800]
[15]
Tice, R.R.; Strauss, G.H. The single cell gel electrophoresis/comet assay: A potential tool for detecting radiation-induced DNA damage in humans. Stem Cells, 1995, 13(Suppl. 1), 207-214.
[PMID: 7488947]
[16]
Dikilitas, M.; Kocyigit, A. Assessment of computerized and manual analysis of slides processed in single cell gel electrophoresis assay. Fresenius Environ. Bull., 2012, 21, 2981-2987.
[17]
Olive, P.L. DNA damage and repair in individual cells: Applications of the comet assay in radiobiology. Int. J. Radiat. Biol., 1999, 75(4), 395-405.
[http://dx.doi.org/10.1080/095530099140311] [PMID: 10331844]
[18]
Collins, A.R. The comet assay for DNA damage and repair: Principles, applications, and limitations. Mol. Biotechnol., 2004, 26(3), 249-261.
[http://dx.doi.org/10.1385/MB:26:3:249] [PMID: 15004294]
[19]
Canady, J.; Arndt, S.; Karrer, S.; Bosserhoff, A.K. Increased KGF expression promotes fibroblast activation in a double paracrine manner resulting in cutaneous fibrosis. J. Invest. Dermatol., 2013, 133(3), 647-657.
[http://dx.doi.org/10.1038/jid.2012.389] [PMID: 23096718]
[20]
Mallavadhani, U.V.; Vanga, N.R.; Jeengar, M.K.; Naidu, V.G.M. Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells. Eur. J. Med. Chem., 2014, 74, 398-404.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.040] [PMID: 24487188]
[21]
Darzynkiewicz, Z. Differential Staining of DNA and RNA in Intact Cells and Isolated Cell Nuclei with Acridine Orange. In: Methods in Cell Biology. Vol.33. Flow Cytometry; Darzynkiewicz, Z.; Crissman, H.A., Eds.; Academic Press: New York, N.Y., 1990; pp. 285-298.
[http://dx.doi.org/10.1016/S0091-679X(08)60532-4]
[22]
Benzie, I.F.F.; Strain, J.J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal. Biochem., 1996, 239(1), 70-76.
[http://dx.doi.org/10.1006/abio.1996.0292] [PMID: 8660627]
[23]
Jiménez-Escrig, A.; Jiménez-Jiménez, I.; Pulido, R.; Saura-Calixto, F. Antioxidant activity of fresh and processed edible seaweeds. J. Sci. Food Agric., 2001, 81(5), 530-534.
[http://dx.doi.org/10.1002/jsfa.842]
[24]
Vandeputte, C.; Guizon, I.; Genestie-Denis, I.; Vannier, B.; Lorenzon, G. A microtiter plate assay for total glutathione and glutathione disulfide contents in cultured/isolated cells: Performance study of a new miniaturized protocol. Cell Biol. Toxicol., 1994, 10(5-6), 415-421.
[http://dx.doi.org/10.1007/BF00755791] [PMID: 7697505]
[25]
Dai, J.; Weinberg, R.S.; Waxman, S.; Jing, Y. Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system. Blood, 1999, 93(1), 268-277.
[http://dx.doi.org/10.1182/blood.V93.1.268] [PMID: 9864170]
[26]
Schoell, W.M.J.; Janicek, M.F.; Mirhashemi, R. Epidemiology and biology of cervical cancer. Semin. Surg. Oncol., 1999, 16(3), 203-211.
[http://dx.doi.org/10.1002/(SICI)1098-2388(199904/05)16:3<203::AID-SSU2>3.0.CO;2-C] [PMID: 10225296]
[27]
Bertram, J.S. The molecular biology of cancer. Mol. Aspects Med., 2000, 21(6), 167-223.
[http://dx.doi.org/10.1016/S0098-2997(00)00007-8] [PMID: 11173079]
[28]
Patel, S.; Gheewala, N.; Suthar, A.; Shah, A. In-vitro cytotoxicity activity of Solanum nigrum extract against Hela cell line and Vero cell line. Int. J. Pharm. Pharm. Sci., 2009, 1, 38-46.
[29]
Jeyaraj, M.; Rajesh, M.; Arun, R.; MubarakAli, D.; Sathishkumar, G.; Sivanandhan, G.; Dev, G.K.; Manickavasagam, M.; Premkumar, K.; Thajuddin, N.; Ganapathi, A. An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using Podophyllum hexandrum on human cervical carcinoma cells. Colloids Surf. B Biointerfaces, 2013, 102, 708-717.
[http://dx.doi.org/10.1016/j.colsurfb.2012.09.042] [PMID: 23117153]
[30]
Palizban, A.A.; Sadeghi-Aliabadi, H.; Abdollahpour, F. Effect of cerium lanthanide on Hela and MCF-7 cancer cell growth in the presence of transferring. Res. Pharm. Sci., 2010, 5(2), 119-125.
[PMID: 21589800]
[31]
Peng, Y.; Guo, C.; Yang, Y.; Li, F.; Zhang, Y.; Jiang, B.; Li, Q. Baicalein induces apoptosis of human cervical cancer HeLa cells in vitro. Mol. Med. Rep., 2015, 11(3), 2129-2134.
[http://dx.doi.org/10.3892/mmr.2014.2885] [PMID: 25373554]
[32]
Fisher, D.E. Apoptosis in cancer therapy: Crossing the threshold. Cell, 1994, 78(4), 539-542.
[http://dx.doi.org/10.1016/0092-8674(94)90518-5] [PMID: 8069905]
[33]
Xie, C.L.; Pan, Y.B.; Hu, L.Q.; Qian, Y.N. Propofol attenuates hydrogenperoxide-induced apoptosis in human umbilical vein endothelial cells via multiple signaling pathways. Korean J. Anesthesiol., 2015, 68(5), 488-495.
[http://dx.doi.org/10.4097/kjae.2015.68.5.488] [PMID: 26495060]
[34]
Hideg, É.; Jansen, M.A.K.; Strid, Å. UV-B exposure, ROS, and stress: Inseparable companions or loosely linked associates? Trends Plant Sci., 2013, 18(2), 107-115.
[http://dx.doi.org/10.1016/j.tplants.2012.09.003] [PMID: 23084465]
[35]
Pelicano, H.; Carney, D.; Huang, P. ROS stress in cancer cells and therapeutic implications. Drug Resist. Updat., 2004, 7(2), 97-110.
[http://dx.doi.org/10.1016/j.drup.2004.01.004] [PMID: 15158766]
[36]
Li, Z.; Yang, Y.; Ming, M.; Liu, B. Mitochondrial ROS generation for regulation of autophagic pathways in cancer. Biochem. Biophys. Res. Commun., 2011, 414(1), 5-8.
[http://dx.doi.org/10.1016/j.bbrc.2011.09.046] [PMID: 21951851]
[37]
Tiloke, C.; Phulukdaree, A.; Chuturgoon, A.A. The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells. BMC Complement. Altern. Med., 2013, 13(1), 226.
[http://dx.doi.org/10.1186/1472-6882-13-226] [PMID: 24041017]
[38]
Ott, M.; Gogvadze, V.; Orrenius, S.; Zhivotovsky, B. Mitochondria, oxidative stress and cell death. Apoptosis, 2007, 12(5), 913-922.
[http://dx.doi.org/10.1007/s10495-007-0756-2] [PMID: 17453160]
[39]
Ueda, S.; Masutani, H.; Nakamura, H.; Tanaka, T.; Ueno, M.; Yodoi, J. Redox control of cell death. Antioxid. Redox Signal., 2002, 4(3), 405-414.
[http://dx.doi.org/10.1089/15230860260196209] [PMID: 12215208]
[40]
Arora, S.; Jain, J.; Rajwade, J.M.; Paknikar, K.M. Cellular responses induced by silver nanoparticles: In vitro studies. Toxicol. Lett., 2008, 179(2), 93-100.
[http://dx.doi.org/10.1016/j.toxlet.2008.04.009] [PMID: 18508209]
[41]
Pan, X.; Zhao, Y.Q.; Hu, F.Y.; Chi, C.F.; Wang, B. Anticancer activity of a hexapeptide from Skate (Raja porosa) cartilage protein hydrolysate in HeLa cells. Mar. Drugs, 2016, 14(8), 153.
[http://dx.doi.org/10.3390/md14080153] [PMID: 27537897]
[42]
Prokhorova, E.A.; Zamaraev, A.V.; Kopeina, G.S.; Zhivotovsky, B.; Lavrik, I.N. Role of the nucleus in apoptosis: Signaling and execution. Cell. Mol. Life Sci., 2015, 72(23), 4593-4612.
[http://dx.doi.org/10.1007/s00018-015-2031-y] [PMID: 26346492]
[43]
Khan, M.; Maryam, A.; Qazi, J.I.; Ma, T. Targeting apoptosis and multiple signaling pathways with icariside II in cancer cells. Int. J. Biol. Sci., 2015, 11(9), 1100-1112.
[http://dx.doi.org/10.7150/ijbs.11595] [PMID: 26221076]
[44]
Tuluce, Y.; Gorgisen, G.; Gulacar, I.M.; Koyuncu, I.; Durgun, M.; Akocak, S.; Ozkol, H.; Kaya, Z. Antiproliferative and apoptotic role of novel synthesized Cu(II) Complex with 3-(3-(4-fluorophenyl)Triaz-1-en-1-yl) benzenesulfonamide in common cancer models. Anticancer Res., 2018, 38(9), 5115-5120.
[http://dx.doi.org/10.21873/anticanres.12832] [PMID: 30194157]
[45]
Tülüce, Y.; Masseh, H.D.I.; Koyuncu, İ.; Kiliç, A.; Durgun, M.; Özkol, H. Novel fluorine boron hybrid complex as potential antiproliferative drugs on colorectal cancer cell line. Anticancer. Agents Med. Chem., 2019, 19(5), 627-637.
[http://dx.doi.org/10.2174/1871520619666190117142353] [PMID: 30652651]
[46]
Koyuncu, I.; Tülüce, Y.; Slahaddin Qadir, H.; Durgun, M.; Supuran, C.T. Evaluation of the anticancer potential of a sulphonamide carbonic anhydrase IX inhibitor on cervical cancer cells. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 703-711.
[http://dx.doi.org/10.1080/14756366.2019.1579805] [PMID: 30810431]
[47]
Tülüce, Y.; Hussein, A.I.; Koyuncu, İ.; Kiliç, A.; Durgun, M. The effect of a bis-structured Schiff base on apoptosis, cytotoxicity, and DNA damage of breast cancer cells. J. Biochem. Mol. Toxicol., 2022, 2022, e23148.
[http://dx.doi.org/10.1002/jbt.23148] [PMID: 35719061]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy