Apoptosis And Genotoxicity Of Selected Β-Carboline Compounds Against Chronic Myelogenous Leukemia Using In Vitro Experimental Models
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Date
2018-04
Authors
Kamaruzaman, Nur Azzalia
Journal Title
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Publisher
Universiti Sains Malaysia
Abstract
β-carboline is known for its numerous traditional uses and has been widely investigated for various health indications. In particular, recently β-carboline has shown some promising findings in the field of anticancer. Hence this study investigates the potential anticancer activity of β-carboline compounds using in vitro models. Thirty synthesized β-carboline compounds were tested using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for anticancer activity and selectivity index (SI) against four human cancer (colon HT-29, cervical HeLa, liver Hep G2 and leukemia K562) and two non-cancer (mouse embryo fibroblasts BALB/c3T3 and human foreskin fibroblasts Hs27) cell lines. Based on the highest selectivity, seven compounds were selected for K562 chronic myelogenous leukemia (CML) cells. A series of experiments were further performed to understand the characteristics of the compounds as well as to investigate their partial mechanism of action in K562 cells. Results from MTT assay have indicated that the selected compounds were able to induce maximal inhibitory activity (IC100) at a range of concentrations from 9.1 μM to 56.9 μM at 48 hours. Furthermore, the compounds acted both as cytostatic and cytocidal agents, when treated at low and high concentrations respectively. Partial mechanism of action studies by acridine orange and ethidium bromide (AO/EB) fluorescence staining and caspase-3 and -7 luminescence assay have shown that the selected compounds induced apoptosis in K562 cells with no upregulation of the caspases, and therefore it could be deduced that non-classical caspase-independent apoptosis was responsible.
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Keywords
Potential anticancer activity of β-carboline compounds , using in vitro models. Thirty synthesized