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

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 structuredependent 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, caspasedependent, apoptotic mechanisms.

Hydroxybenzoate magnesium analogues induced apoptosis in HT-1080 human fibrosarcoma cells

“…Therefore, the several attempts were carried out to design derivatives that focus on improving aspirin efficacy. Our previous research indicated that the designed new salicylate analogues reduced the effective dose of aspirin and induced apoptosis in different cell lines, including fibrosarcoma, breast cancer, and primary chronic lymphatic leukaemia (CLL) [3][4][5][6]. These compounds include hydroxybenzoate Na, Ca, and Zn, (Figure 1), 4-HBZn was the most effective anti-cancer agent [4,6].…”

“…Our previous research indicated that the designed new salicylate analogues reduced the effective dose of aspirin and induced apoptosis in different cell lines, including fibrosarcoma, breast cancer, and primary chronic lymphatic leukaemia (CLL) [3][4][5][6]. These compounds include hydroxybenzoate Na, Ca, and Zn, (Figure 1), 4-HBZn was the most effective anti-cancer agent [4,6]. In this respect, zinc 4-HBZn reduced cell viability, arrested cell cycle in G0/G1 and regulated apoptosis via intrinsic pathway [3,7].…”