THE ANTICANCER POTENTIAL OF THYMOQUINONE IS ENHANCED IN BREAST CANCER CELLS ENRICHED WITH COPPER

الموضوعات

علوم بحتة وطبيعية

الملخص

Cellular and serum levels of copper are seen to be upregulated in many cancer typesincluding aggressive breast cancer. High copper levels aid aggressive breast cancer inmultiple facets including angiogenesis and proliferation signalling. Thymoquinone (TQ)the bioactive constituent of Black Seed has displayed promising antioxidant and antiproliferative effects in many cancer types both in vitro and in vivo. Further, TQ wasdemonstrated to be a copper redox modulator able to induce oxidative DNA breakage incells via the mobilization of endogenous copper ions. However, the effect of TQ on breastcancer displaying increased copper levels is unknown. Here, we investigated theanticancer potential of TQ on two breast cancer cell lines MDA-MB-231 and MCF-7 cellsenriched with copper to mimic the in vivo conditions. The effect of TQ on the viabilityand cell cycle progression of both cell lines cultured in normal and increased copperconditions was evaluated by MTT assay and flow cytometry, respectively. In addition,reactive oxygen species generation after TQ treatment was assessed by DCFDH assayand PARP expression was evaluated by Western blot. This study is the first to reportincreased cytotoxic effects of TQ in breast cancer cells enriched with copper. TQ aloneinhibited cell viability in a dose-dependent manner in both MDA-MB-231 and MCF-7cell lines. The IC50 values of TQ were 32 µM and 46 µM in MDA- MB-231 and MCF-7cell lines respectively at 24 hours post treatment with TQ in low copper conditions. IC50values dropped to 10 µM and 38 µM for MDA_MB-231 and MCF-7 cells respectivelywhen in high copper conditions. TQ caused greater inhibition of cell viability, increasedsub-G1 cells and elevated ROS generation when both cell lines were enriched with coppercompared to those cultured in normal copper conditions. Pre-treatment with N-acetylcysteine (NAC) abrogated the inhibitory effect of TQ on cell viability and cell cycledistribution suggesting that cell death is ROS dependent. In conclusion, our resultssuggest that the anticancer efficacy of TQ was further enhanced in breast cancer cellscontaining high copper. Further studies are needed to elucidate the role of copper in theanticancer mechanism of TQ and explore TQ ability to selectively induce cell death incancer cells while sparing normal cells having normal copper level.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0cf54a7e-95c6-475a-b7a9-c27e1de15195

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

2325938_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":" Hala Muhtasib ","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"James Maurice Abbas","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

THE ANTICANCER POTENTIAL OF THYMOQUINONE IS ENHANCED IN BREAST CANCER CELLS ENRICHED WITH COPPER

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

Show simple item record dc.contributor.advisor Muhtasib, Hala dc.contributor.author Abbas, James dc.date.accessioned 2023-08-16T10:34:59Z dc.date.available 2023-08-16T10:34:59Z dc.date.issued 2023-08-16 dc.date.submitted 2023-08-14 dc.identifier.uri http://hdl.handle.net/10938/24118 dc.description.abstract Cellular and serum levels of copper are seen to be upregulated in many cancer typesincluding aggressive breast cancer. High copper levels aid aggressive breast cancer inmultiple facets including angiogenesis and proliferation signalling. Thymoquinone (TQ)the bioactive constituent of Black Seed has displayed promising antioxidant and antiproliferative effects in many cancer types both in vitro and in vivo. Further, TQ wasdemonstrated to be a copper redox modulator able to induce oxidative DNA breakage incells via the mobilization of endogenous copper ions. However, the effect of TQ on breastcancer displaying increased copper levels is unknown. Here, we investigated theanticancer potential of TQ on two breast cancer cell lines MDA-MB-231 and MCF-7 cellsenriched with copper to mimic the in vivo conditions. The effect of TQ on the viabilityand cell cycle progression of both cell lines cultured in normal and increased copperconditions was evaluated by MTT assay and flow cytometry, respectively. In addition,reactive oxygen species generation after TQ treatment was assessed by DCFDH assayand PARP expression was evaluated by Western blot. This study is the first to reportincreased cytotoxic effects of TQ in breast cancer cells enriched with copper. TQ aloneinhibited cell viability in a dose-dependent manner in both MDA-MB-231 and MCF-7cell lines. The IC50 values of TQ were 32 µM and 46 µM in MDA- MB-231 and MCF-7cell lines respectively at 24 hours post treatment with TQ in low copper conditions. IC50values dropped to 10 µM and 38 µM for MDA_MB-231 and MCF-7 cells respectivelywhen in high copper conditions. TQ caused greater inhibition of cell viability, increasedsub-G1 cells and elevated ROS generation when both cell lines were enriched with coppercompared to those cultured in normal copper conditions. Pre-treatment with N-acetylcysteine (NAC) abrogated the inhibitory effect of TQ on cell viability and cell cycledistribution suggesting that cell death is ROS dependent. In conclusion, our resultssuggest that the anticancer efficacy of TQ was further enhanced in breast cancer cellscontaining high copper. Further studies are needed to elucidate the role of copper in theanticancer mechanism of TQ and explore TQ ability to selectively induce cell death incancer cells while sparing normal cells having normal copper level. dc.language.iso en dc.subject Cancer, Thymoquinone, copper, oxidative DNA Damage, Apoptosis, Reactive Oxygen Species

إشراف وإعداد

الإشراف

Hala Muhtasib

الإعداد

James Maurice Abbas

الاقتباسات الببليوغرافية