{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:26:51Z","timestamp":1791318411827,"version":"4.3.1"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education (MOHE) Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2020\/STG02\/UKM\/03\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/STG02\/UKM\/03\/1"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The discovery of cisplatin has influenced scientists to study the anticancer properties of other metal complexes. Organotin(IV) dithiocarbamate compounds are gaining attention as anticancer agents due to their potent cytotoxic properties on cancer cells. In this study, a series of organotin compounds were assessed for their toxic effects on the Jurkat E6.1 cell line. WST-1 assay was used to determine the cytotoxic effect of the compounds and showed that six out of seven organotin(IV) dithiocarbamate compounds exhibited potent cytotoxic effects toward T-lymphoblastic leukemia cells, Jurkat E6.1 with the concentration of IC50 ranging from 0.67\u20130.94 \u00b5M. The apoptosis assay by Annexin V-FITC\/PI staining showed that all tested compounds induced cell death mainly via apoptosis. Cell cycle analysis assessed using RNase\/PI staining showed that organotin(IV) dithiocarbamate compounds induced cell cycle arrest at different phases. In conclusion, the tested organotin(IV) dithiocarbamate compounds demonstrated potent cytotoxicity against Jurkat E6.1 cells via apoptosis and cell cycle arrest at low IC50 value. However, further studies on the mechanisms of action are required to probe the possible potential of these compounds on leukemia cells before they can be developed into anti-leukemic agents.<\/jats:p>","DOI":"10.3390\/molecules28083376","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:08:11Z","timestamp":1681265291000},"page":"3376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Series of Organotin(IV) Compounds with Different Dithiocarbamate Ligands Induced Cytotoxicity, Apoptosis and Cell Cycle Arrest on Jurkat E6.1, T Acute Lymphoblastic Leukemia Cells"],"prefix":"10.3390","volume":"28","author":[{"given":"Nur Rasyiqin","family":"Rasli","sequence":"first","affiliation":[{"name":"Program of Biomedical Science, Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-9453","authenticated-orcid":false,"given":"Asmah","family":"Hamid","sequence":"additional","affiliation":[{"name":"Program of Biomedical Science, Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normah","family":"Awang","sequence":"additional","affiliation":[{"name":"Program of Environmental Health and Industrial Safety, Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Farahana","family":"Kamaludin","sequence":"additional","affiliation":[{"name":"Program of Environmental Health and Industrial Safety, Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-63528-0","article-title":"Rates and trends of childhood acute lymphoblastic leukaemia: An epidemiology study","volume":"10","author":"Kakaje","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_2","unstructured":"Puckett, Y., and Chan, O. (2017). Treasure Island, StatPearls."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1158\/1055-9965.EPI-18-0801","article-title":"Is There Etiologic Heterogeneity between Subtypes of Childhood Acute Lymphoblastic Leukemia? A Review of Variation in Risk by SubtypeLiterature Review of Childhood ALL Risk Variation by Subtype","volume":"28","author":"Williams","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e838","DOI":"10.1038\/cddis.2013.350","article-title":"Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment","volume":"4","author":"Sui","year":"2013","journal-title":"Cell DeathDis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1166\/jbn.2018.2530","article-title":"Vincristine-loaded and sgc8-modified liposome as a potential targeted drug delivery system for treating acute lymphoblastic leukemia","volume":"14","author":"Duan","year":"2018","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev-pharmtox-010715-103111","article-title":"Toward a better understanding of the complexity of cancer drug resistance","volume":"56","author":"Gottesman","year":"2016","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102925","DOI":"10.1016\/j.bioorg.2019.102925","article-title":"Cisplatin: The first metal based anticancer drug","volume":"88","author":"Ghosh","year":"2019","journal-title":"Bioorganic. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.5114\/wo.2015.54386","article-title":"Noble metals in oncology","volume":"19","author":"Markowska","year":"2015","journal-title":"Contemp. Oncol.\/Wsp\u00f3\u0142czesna Onkol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10565-010-9178-y","article-title":"Cytotoxic effects of two organotin compounds and their mode of inflicting cell death on four mammalian cancer cells","volume":"27","author":"Costanzo","year":"2011","journal-title":"Cell Biol. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.molstruc.2018.11.022","article-title":"Synthesis, characterization, and cytotoxicity study of organotin (IV) complexes involving different dithiocarbamate groups","volume":"1179","author":"Adeyemi","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.13005\/ojc\/330420","article-title":"Cytotoxicity assessment of organotin (IV)(2-metoxyethyl) methyldithiocarbamate compounds in human leukemia cell lines","volume":"33","author":"Kamaludin","year":"2017","journal-title":"Orient. J. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/aoc.3362","article-title":"Diphenyltin (IV) dithiocarbamate macrocyclic scaffolds as potent apoptosis inducers for human cancer HEP 3B and IMR 32 cells: Synthesis, spectral characterization, density functional theory study and in vitro cytotoxicity","volume":"29","author":"Kadu","year":"2015","journal-title":"Appl. Organomet. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.17576\/jsm-2020-4906-20","article-title":"Cytotoxic Effects of Organotin (IV) Dithiocarbamate Compounds with Different Functional Groups on Leukemic Cell Line, K-562 (Kesan Sitotoksik Sebatian Organotin (IV) Ditiokarbamat Berlainan Kumpulan Fungsian pada Sel Titisan Leukemia, K-562)","volume":"49","author":"Hamid","year":"2020","journal-title":"Sains Malays."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/cbin.11137","article-title":"Cell death: A review of the major forms of apoptosis, necrosis and autophagy","volume":"43","year":"2019","journal-title":"Cell Biol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41571-020-0341-y","article-title":"Targeting apoptosis in cancer therapy","volume":"17","author":"Carneiro","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_16","first-page":"315","article-title":"Apoptosis: Physiological cell death and its role in pathogenesis of diseases","volume":"37","year":"2003","journal-title":"Neurol. I Neurochir. Pol."},{"key":"ref_17","unstructured":"Prasad, S.B. (2022). Understanding Cancer, Elsevier."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1038\/s41388-018-0555-y","article-title":"Tissue necrosis and its role in cancer progression","volume":"38","author":"Feiglin","year":"2019","journal-title":"Oncogene"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/sj.jid.5700629","article-title":"The effects of dickkopf 1 on gene expression and Wnt signaling by melanocytes: Mechanisms underlying its suppression of melanocyte function and proliferation","volume":"127","author":"Yamaguchi","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1158\/0008-5472.CAN-17-2782","article-title":"Development of Chemotherapy with Cell-Cycle Inhibitors for Adult and Pediatric Cancer Therapy Combination Therapies for Cancer","volume":"78","author":"Mills","year":"2018","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1107\/S2056989020000122","article-title":"(N, N-Diallyldithiocarbamato-\u03ba2S, S\u2032) triphenyltin (IV) and bis (N, N-diallyldithiocarbamato-\u03ba2S, S\u2032) diphenyltin (IV): Crystal structure, Hirshfeld surface analysis and computational study","volume":"76","author":"Haezam","year":"2020","journal-title":"Acta Crystallogr. Sect. E Crystallogr. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.sjbs.2021.02.060","article-title":"Synthesis and cytotoxic activity of organotin (IV) diallyldithiocarbamate compounds as anticancer agent towards colon adenocarcinoma cells (HT-29)","volume":"28","author":"Haezam","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1080\/00958972.2015.1046849","article-title":"Synthesis, characterization, biological activities, crystal structure and DNA binding of organotin (IV) 5-chlorosalicylates","volume":"68","author":"Hussain","year":"2015","journal-title":"J. Coord. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"768","DOI":"10.3923\/pjbs.2011.768.774","article-title":"Cytotoxic effect of organotin (IV) benzylisopropyldithiocarbamate compounds on Chang liver cell and hepatocarcinoma HepG2 cell","volume":"14","author":"Awang","year":"2011","journal-title":"Pak. J. Biol. Sci. PJBS"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1021\/cr900134a","article-title":"Application of metal coordination chemistry to explore and manipulate cell biology","volume":"109","author":"Haas","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_26","unstructured":"World Health Organization (2006). Mono-and Disubstituted Methyltin, Butyltin, and Octyltin Compounds, World Health Organization."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.scitotenv.2019.06.440","article-title":"Toxicity of perfluorinated compounds to soil microbial activity: Effect of carbon chain length, functional group and soil properties","volume":"690","author":"Cai","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_28","first-page":"323","article-title":"Dithiocarbamate toxicity-an appraisal","volume":"2011","author":"Rath","year":"2011","journal-title":"Pestic. Mod. World\u2014Eff. Pestic. Expo."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.microc.2019.01.030","article-title":"The impact of lipophilicity on environmental processes, drug delivery and bioavailability of food components","volume":"146","author":"Chmiel","year":"2019","journal-title":"Microchem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15584","DOI":"10.3390\/molecules191015584","article-title":"Cellular transport mechanisms of cytotoxic metallodrugs: An overview beyond cisplatin","volume":"19","author":"Spreckelmeyer","year":"2014","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3923\/pjbs.2013.12.21","article-title":"Synthesis, characterization and crystal structure of organotin (IV) N-butyl-N-phenyldithiocarbamate compounds and their cytotoxicity in human leukemia cell lines","volume":"16","author":"Kamaludin","year":"2013","journal-title":"Pak. J. Biol. Sci. PJBS"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"007","DOI":"10.7324\/JAPS.2015.54.S2","article-title":"In vitro cytotoxic activity of new triphenyltin (IV) alkyl-isopropyl-di-thiocarbamate compounds on human acute T-lymphoblastic cell line","volume":"5","author":"Awang","year":"2015","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Resnik, R.R., and Resnik, R.J. (2018). Misch\u2019s Avoiding Complications in Oral Implantology, Elsevier.","DOI":"10.1016\/B978-0-323-37580-1.00017-2"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bartma\u0144ska, A., Tronina, T., Pop\u0142o\u0144ski, J., Milczarek, M., Filip-Psurska, B., and Wietrzyk, J. (2018). Highly cancer selective antiproliferative activity of natural prenylated flavonoids. Molecules, 23.","DOI":"10.3390\/molecules23112922"},{"key":"ref_35","first-page":"39","article-title":"Multiple cell death modalities and their key features","volume":"2","author":"Yan","year":"2020","journal-title":"World Acad. Sci. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ianevski, A., Kulesskiy, E., Krpina, K., Lou, G., Aman, Y., Bugai, A., Aasumets, K., Akimov, Y., Bulanova, D., and Gildemann, K. (2020). Chemical, physical and biological triggers of evolutionary conserved Bcl-xL-mediated apoptosis. Cancers, 12.","DOI":"10.1101\/2020.01.13.904714"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5750","DOI":"10.1021\/acs.jmedchem.8b01668","article-title":"Inhibitor of apoptosis protein (IAP) antagonists in anticancer agent discovery: Current status and perspectives","volume":"62","author":"Cong","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"021502","DOI":"10.1063\/1.3292206","article-title":"DNA damage and mitochondria dysfunction in cell apoptosis induced by nonthermal air plasma","volume":"96","author":"Kim","year":"2010","journal-title":"Appl. Phys. Lett."},{"key":"ref_39","first-page":"3358","article-title":"An organotin indomethacin derivative inhibits cancer cell proliferation and synergizes the antiproliferative effects of lapatinib in breast cancer cells","volume":"10","author":"Barrera","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_40","unstructured":"Kumar, R., Saneja, A., and Panda, A.K. (2021). Lung Cancer, Springer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-immunol-042617-053010","article-title":"Apoptosis and clearance of apoptotic cells","volume":"36","author":"Nagata","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2013.12.026","article-title":"Biomarkers of liver cell death","volume":"60","author":"Eguchi","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/cbf.1774","article-title":"Apoptosis: Why and how does it occur in biology?","volume":"29","author":"Ulukaya","year":"2011","journal-title":"Cell Biochem. Funct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/cr.2017.133","article-title":"Plasma membrane changes during programmed cell deaths","volume":"28","author":"Zhang","year":"2018","journal-title":"Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1039\/C5MB00791G","article-title":"In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin (iv) complex","volume":"12","author":"Martins","year":"2016","journal-title":"Mol. BioSyst."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.biopha.2015.02.027","article-title":"Diorganotin (IV) complexes with 4-nitro-N-phthaloyl-glycine: Synthesis, characterization, antitumor activity and DNA-binding studies","volume":"71","author":"Yan","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1107\/S2056989019012490","article-title":"(N, N-Diisopropyldithiocarbamato) triphenyltin (IV): Crystal structure, Hirshfeld surface analysis and computational study","volume":"75","author":"Haezam","year":"2019","journal-title":"Acta Crystallogr. Sect. E Crystallogr. Commun."},{"key":"ref_48","first-page":"675","article-title":"Crystal structure of dimethylbis (diisopropyldithiocarbamato-\u03ba2S, S\u2032) tin (IV), C16H34N2S4Sn","volume":"235","author":"Haezam","year":"2020","journal-title":"Z. F\u00fcr Krist.-New Cryst. Struct."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/8\/3376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:08Z","timestamp":1760123648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/8\/3376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["molecules28083376"],"URL":"https:\/\/doi.org\/10.3390\/molecules28083376","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]}}}