Document Details
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Document Type |
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Thesis |
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Document Title |
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ANTI-BREAST CANCER PROFILING FOR TAFURAMYCIN-A ALONE AND IN COMBINATION WITH NATURALLY OCCURRING COMPOUNDS تقييم لتاثير مركب التافورامايسن-أ كمضاد لسرطان الثدي منفردا ومع بعض المركبات الطبيعية |
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Subject |
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faculty of science |
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Document Language |
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Arabic |
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Abstract |
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Tafuramycin-A (TAF) is naturally occurring duocarmycin-SA derivative with known DNA alkylating and/or intercalating potential. On the other hand, TAF possesses excessive and non-specific toxic properties. Epicatechin (EPI) and thymoquinone (TQ) are naturally occurring compounds with a wide range biological activities, such as anticancer and chemomodulatory potentials. Herein, we temporally assessed the anti-breast cancer properties of TAF alone and in combination with EPI or TQ against naïve (MCF-7, MDA-MB-231 and T47D cells) and resistant breast cancer cells (MCF-7/ADR). TAF alone showed very potent cell killing properties against both naïve and resistant breast cancer cell lines in a time dependent manner with IC 50 ’s ranging from 17 - 190 nM, 2 - 19 nM and 1 - 2 nM after 24 h, 48 h and 72 h exposures, respectively. To a lesser extent, TQ alone showed moderate cytotoxic properties against all cell lines in a time dependent manner with IC 50 ’s ranging from 4.4 – 18.9 µM, 2.8 – 16.5 µM and 2.1 – 22.7 µM after 24 h, 48 h and 72 h exposures, respectively. EPI was the weakest in comparison to the previous two agents with IC 50 ’s above 100 µM in all cell line in all durations of exposure. Equitoxic combinations of TAF with TQ showed antagonistic interaction in all cells under investigation with combination indices ranging from 1- 93, 1- 95 and 2-99 nM at 24 h in MCF-7, MCF-7/ADR, T47D , respectively. Except 24 h exposure of MDA-MB-231 cells, combinations of TAF with TQ showed synergistic interaction from 190 to 81 nM. Combination of TAF with 10 µM EPI did not induce any prominent enhancement in TAF cytotoxic properties. Cell cycle analysis using DNA content flowcytometry showed moderate S-phase and G 2 /M-phase partial arrest in response to treatment with TAF, TQ and their combinations. While treatment with EPI induced significant arrest in G 0 /G 1 -phase which is similar of its reported anti-proliferative activity. Further analysis for the differential apoptosis/necrosis cell death using annexin-V/FITC with PI counterstain and coupled with flowcytometric analysis showed significant necrosis induction of TAF alone against breast cancer cells under investigation. Yet, combination of TAF with TQ or EPI decreased the percentage of necrosis induced by TAF alone; however, it induced significant apoptosis cell death. Yet, explanation for shifting breast cancer cell death from necrosis to apoptosis due to combination of TAF with TQ or EPI is currently under molecular investigation and might constitute high potential in utilizing TAF for the treatment of breast cancer. |
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Supervisor |
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Prof. Fahad Ahmed Mohamed Al-Abbasi |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1441 AH
2020 AD |
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Co-Supervisor |
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Prof. Abdulwahab Noorwali |
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Added Date |
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Wednesday, February 26, 2020 |
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Researchers
| عهود يحيى الشهري | Alshehri, Ohoud Yahya | Researcher | Doctorate | |
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