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Title: 2-Hydroxybenzoate analogue mediated apoptosis in human HT-1080 fibrosarcoma cells
Author: Alkarrawi, Mohammed
ISNI:       0000 0004 2748 2900
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2005
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The antitumour activities of 18 benzoic acid and 2-hydroxybenzoic acid analogues were investigated in HT-1080 fibrosarcoma cell line. Several approaches were used to identify the most effective apoptotic agents capable of inhibiting cell population expansion of HT-1080 cells mostly at a concentration of 0.4mM. Techniques used in this study included: cell viability assays (MTT, direct count and time-lapse tracking images), morphology (DAPI, haematoxylin-eosin, methyl green-pyronin y, and SEM), immunocytochemistry (Annexin V, caspase-3) and pharmacology (2-hydroxybenzoate uptake). The results indicated that most of these compounds showed antiproliferative activities at specific concentrations (range 0.025-8mM), with an incubation time of 2-180 hours. It is evident that zinc 2-hydroxybenzoate was the most effective antiproliferative agent at 0.3 and 0.4mM. Other analogues, mainly calcium, also showed antiproliferative activities but at higher concentrations (up to 8mM). The growth inhibitory effect on HT-1080 cells population after treatment with either calcium or zinc 2-hydroxybenzoates was identified as the occurrence of apoptosis. This was confirmed by the morphological techniques as well as by immunoassay including annexin V and caspase- 3, measured by flow cytometry. Although strong evidence has been presented here for apoptosis, the genetic mechanism remains uncertain. Neither the expression of the six proteins p53, p21, Bax, Bcl-2, histones and TNF-a, nor the cell cycle analysis was able to fully elucidate the mechanism of action of calcium and zinc 2-hydroxybenzoate on HT-1080 cells. Nonetheless, calcium and zinc 2-hydroxybenzoate-induced apoptosis clearly involved caspase-3 through Bax and p53/p21, respectively, and displayed the properties of potentially therapeutic compounds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available