|
Document Type |
: |
Thesis |
|
Document Title |
: |
Effect of Some Compounds of Natural Origin on GIT Cancer Cells تأثير بعض المركبات ذات المنشأ الطبيعي على خلايا سرطان الجهاز الهضمي |
|
Subject |
: |
Faculty of Medicine |
|
Document Language |
: |
Arabic |
|
Abstract |
: |
The use of adjuvant anti-cancer therapy is justified by increasing the effectiveness of therapy, and/or reducing the side effects of chemotherapeutics. Colossolactone-G is a naturally occurring triterpenoid metabolite isolated from the fruiting body of Ganoderma colossum. In this study, we evaluated the potential chemo modulatory effects of colossolactone-G to 5-fluorouracil and gemcitabine against human colorectal cancer cells. After 72 h of exposure, colossolactone-G solely possessed cytotoxic effects against HCT116 and HT29 cells with IC50’s of 22.29±11.9 µM and 90.5±1.7 µM, respectively. Likewise, colossolactone-G improved the cytotoxic profile of Gemcitabine against HCT116 and HT-29 cells by reducing its IC50 from 0.28±0.1 µM to 19.41±3.1 nM with combination index indicative of synergism (CI-value = 0.154) and from 6.2±1.1 µM to 0.6±0.3 µM (CI-value = 0.219), respectively. Moreover, colossolactone-G synergized the cytotoxic profile of 5-fluorouracil against HCT116 and HT29 cells decreasing its IC50’s from 10.75±4.6 µM to 3.10±0.4 nM (CI-value = 0.014), and from 12.88±3.74 µM to 3.2±0.6 µM (CI-value = 0.427), respectively. By evaluating cell cycle distribution using DNA content flowcytometry, both gemcitabine and 5-fluorouracil induced moderate cell cycle arrest at S-phase, which was increased by combination with colossolactone-G and was further extended to induce accumulation of cells at G0/G1-phase. Longer exposure of cells to colossolactone-G alone induced antiproliferative effect and accumulation of cells at G0/G1-phase. Cell cycle arrest attributed to gemcitabine and 5-fluorouracil treatment resulted in increasing cells undergoing apoptosis as shown by annexin-V/FITC staining. Similarly, combination increased percentage of cells undergoing autophagy in both cell lines. In conclusion, colossolactone-G represents promising chemomodulatory compound of natural origin, which enhance the anti-colorectal cancer activity of gemcitabine and 5-fluorouracil |
|
Supervisor |
: |
Dr. Gehan Hegazy |
|
Thesis Type |
: |
Master Thesis |
|
Publishing Year |
: |
1440 AH
2019 AD |
|
Co-Supervisor |
: |
Dr. Ahmed Mohamed Al-Abd |
|
Added Date |
: |
Tuesday, May 7, 2019 |
|
Researchers
| ريناد علي الجهني | Aljohani, Rinad Ali | Researcher | Master | |
|