Document Details

Document Type : Thesis 
Document Title :
Study the impact of loading 2-methoxyestradiol on nanoparticles and its cytotoxicity in breast cancer cells
دراسة أثر تحميل ٢-ميثوكسي أستراديول في جسيمات نانونية على سميته الخلوية في خلايا سرطان الثدي
 
Subject : Faculty of Science 
Document Language : Arabic 
Abstract : 2-Methoxyestradiol (2ME) is an estrogen metabolite that possesses promising antiproliferative and cytotoxic activities. However, it suffers unfavorable pharmaco-kinetic characteristics. The aim of this study was to prepare an optimized 2ME self-nanoemulsifying drug delivery system (2ME-SNEDDS) and evaluate its cytotoxicity and proapoptotic activities in the breast cancer cells, MCF-7. For optimization of 2ME-SNEDDS, a three-component system was used in the D-optimal mixture experimental study. MCF-7 cells were incubated with 2ME-SNEDDS and subjected to assessment of growth inhibition, cell cycle progression, annexin V staining, caspase-3 concentration, Bax, Bcl-2, and CyclinD1 mRNA expression, and reactive oxygen species (ROS) production. The results showed that the optimized formula had a globule size of 94.97 ± 4.35 nm, Zetapotential was -3.4 ±1.2 with PDI 0.34, in addition to 96.3 ± 4.3% of 2ME was released from 2ME-SNEDDS within 24 h using activated analysis bag technique. Also, the prepared 2ME-SNEDDS exhibited significant enhancement of cytotoxicity against MCF-7 cells in comparison to raw 2ME. This was associated with cyclin D1 expression down-regulation and increase of cells in G0/G1 and G2/M phases. The pro-apoptotic activities of 2ME-SNEDDS were confirmed by annexin V staining which indicated enhanced early and late cell death. This is accompanied by modulation of mRNA expression of Bax and Bcl2 in favor of apoptosis. 2ME-SNEDDS significantly enhanced cleaved caspase-3 concentration in comparison to raw 2ME. In addition, 2ME-SNEDDS significantly elevated the generation of ROS in MCF7 cells. In conclusion, 2ME-SNEDDS exhibits enhanced cytotoxicity and pro-apoptotic activity in MCF-7 cells. This can be attributed to, at least partially, ROS generation. 
Supervisor : Prof. Fahad Ahmed Mohammed Al-Abbasi 
Thesis Type : Doctorate Thesis 
Publishing Year : 1445 AH
2023 AD 
Co-Supervisor : Prof. Ashraf Bayeldin Abdel-Naim 
Added Date : Tuesday, November 28, 2023 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
سلوى ظافر القحطانيAl-Qahtani, Salwa DhafferResearcherDoctorate 

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