Publication:
Apoptosis activities of nickel and copper complexes from thymoquinone and dithiocarbamate on oral cancer cell lines in vitro

dc.contributor.affiliation#PLACEHOLDER_PARENT_METADATA_VALUE#en_US
dc.contributor.authorSuriyah, Wastuti Hidayatien_US
dc.date.accessioned2024-10-09T07:19:56Z
dc.date.available2024-10-09T07:19:56Z
dc.date.issued2018
dc.description.abstractOral squamous cell carcinoma (OSCC) has been associated with high morbidity and mortality rate. Metal-based anticancer drugs such as platinum-based agents have been widely used to treat various cancer cells including OSCC. However, their efficiency is limited by the side effects and frequent development of chemoresistant cancer cells. To date, research on metal-based compounds has been extensively continued to develop more promising chemotherapeutic compounds capable to overcome these limitations. Thymoquinone (TQ) has been reported to have numerous biological activities, including anticancer in vitro and in vivo. Similarly, dithiocarbamate (PEDTC) is also known to have in vitro antineoplastic potential against several types of cell lines. Nickel and copper complexes from TQ (NiTQPy, CuTQPy) and PEDTC (NiPEDTC, CuPEDTC) were successfully synthesized and characterized. These metal complexes provide new approach to broaden the spectrum of biological activities their parent ligands. The study is aimed to investigate and determine anticancer potential of the metal complexes derived from TQ and PEDTC. Human OSCC HSC-3 and HSC-4 cell lines were chosen as in vitro model. The cells were exposed to various concentrations of the compound substances and examined by MTT assay for cytotoxicity analysis. Normal human oral fibroblast and human keratinocyte (HACAT) cells were also included in the assay. Zebrafish was used as a model for in vivo toxicity study. The number of apoptotic cells was quantified by flow cytometry and confirmed by Caspase 3/7 assay. Quantitative RT PCR was performed to analyze the mRNA expression of apoptotic-regulator genes. The protein expression was observed by western blot. The MTT assay demonstrated that the metal complexes induced cytotoxicity on HSC-3 and HSC-4 cells. Exposure of the metal complexes at the concentration similar to cancer cells relatively did not affect the normal cells and zebrafish embryo development, except for those treated with copper complexes. Flow cytometry showed the metal complexes increased the number of sub-G1 population, which represent apoptotic cells. The apoptotic activities were supported by Caspase 3/7 analysis. The various degree of apoptosis induction by metal complexes from TQ and PEDTC are associated with the elevation of BAX/BCL-2 ratio in both transcriptional (mRNA) and translational (protein) levels. NiPEDTC and NiTQPy was shown to be the most effective to induce apoptosis in HSC-3 and HSC-4 cells among the metal complexes. To conclude, these models of study are useful to demonstrate apoptosis activities in OSCC. The metal complexes from TQ and PEDTC are suggested to merit further investigation for its potentiation as anticancer agents.en_US
dc.description.callnumbert RS 431 A64 S961A 2018en_US
dc.description.degreelevelDoctoralen_US
dc.description.identifierThesis : Apoptosis activities of nickel and copper complexes from thymoquinone and dithiocarbamate on oral cancer cell lines in vitro /by Wastuti Hidayati Suriyahen_US
dc.description.identityt11100396852WastutiHidayatiSuriyahen_US
dc.description.kulliyahKulliyyah of Pharmacyen_US
dc.description.notesThesis (Ph.D)--International Islamic University Malaysia, 2018.en_US
dc.description.physicaldescriptionxxiii, 177 leaves :colour illustrations ;30cm.en_US
dc.description.programmeDoctor of Philosophy in Pharmaceutical Sciences (Pharmacology)en_US
dc.identifier.urihttps://studentrepo.iium.edu.my/handle/123456789/11059
dc.identifier.urlhttps://lib.iium.edu.my/mom/services/mom/document/getFile/l85l10XwfWK9l1zs5r3vStXt8lhbZ1FS20190411104208859
dc.language.isoenen_US
dc.publisherKuantan, Pahang :International Islamic University Malaysia,2018en_US
dc.rightsCopyright International Islamic University Malaysia
dc.subject.lcshAntineoplastic agentsen_US
dc.subject.lcshApoptosisen_US
dc.subject.lcshCancer -- Alternative treatmenten_US
dc.titleApoptosis activities of nickel and copper complexes from thymoquinone and dithiocarbamate on oral cancer cell lines in vitroen_US
dc.typeDoctoral Thesisen_US
dspace.entity.typePublication

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