Table of Contents
Journal of Cancer Research
Volume 2013, Article ID 203659, 8 pages
http://dx.doi.org/10.1155/2013/203659
Research Article

The Effect of Hydroxybenzoate Lithium Complexes in Inducing Apoptosis in HT-1080 Human Fibrosarcoma Cells

1College of Medicine, Shaqra University, Riyadh 11691, Saudi Arabia
2School of Medicine, Cochrane Medical Education Centre, Heath Park, Cardiff CF14 4YU, UK
3Zoology Department, King Saud University, Riyadh 11495, Saudi Arabia
4Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK

Received 26 March 2013; Revised 7 July 2013; Accepted 19 July 2013

Academic Editor: Shoji Natsugoe

Copyright © 2013 Jassem G. Mahdi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There has been a growing interest in the beneficial effects of simple phenolic acids and their ability to exhibit various biological activities. The aim of this study was to assess in vitro biological activities of 2-, 3-, and 4-hydroxybenzoate lithium (HBLi) complexes on HT-1080 human fibrosarcoma cells by methods of using a metabolic activity assay, immunochemical and morphological techniques. Results showed that HBLi complexes exert their cytotoxic activities in a concentration- and chemical structure-dependent manner in the following order: 4-HBLi > 3-HBLi > 2-HBLi. Flow cytometry displayed evidence of apoptosis induced by 3-HBLi (21.8%) and 4-HBLi (33.2%). These results were verified by SEM, which revealed the formation of apoptotic bodies. In addition, these 3-HBLi and 4-HBLi caused an increase in HT-1080 cell cycle arrest in G0/G1 phase when compared to the controls (25% and 30.6%, resp.) when cells were treated with 6 mM for 24 hours. Immunochemical studies related to the molecular mechanism of apoptosis indicated that HBLi complexes downregulated the expression of Bcl-2 and upregulated Bax, p53, and caspases-3 in a concentration-dependent manner. HBLi complexes lowered Bcl-2/Bax ratios and induced the expression of p53 and caspase-3. These results suggest that HBLi complexes may exert their apoptotic effects through mitochondrial-mediated, caspase-dependent, apoptotic mechanisms.