Abstract
BackgroundLung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells.MethodsMTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting.ResultsAA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells.ConclusionsAspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.
Highlights
Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities
The cells on the upper side of the membrane were removed with cotton swabs, and the cells attached to the Cytotoxicity of Aspiletrein A (AA) on H460, H23 and A549 human lung cancer cells A previous study demonstrated that AA exhibited the strongest cytotoxicity among isolated saponins and exerted potent effects against the LU-1 cell line, with an 50% Inhibitory concentration (IC50) value of 9.94 ± 2.15 μM [25]
The selectivity index calculated as the IC50 of normal cells/IC50 of cancer cells, demonstrated that AA has a selectivity index in the range of 1.7–2.9, indicating that this compound preferentially induced cytotoxicity in lung cancer
Summary
Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. Elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. Several signaling pathways governing cancer aggressiveness, including protein kinase B (Akt), have been identified. An increase in active Akt or its phosphorylation (pAkt) enhances the cell growth, cell survival and metastasis abilities of lung cancer, and the attenuation of Akt function has become a promising strategy for the research and development of anti-lung cancer therapies [12]. The discovery of novel anticancer agents for lung cancer is urgently required
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