Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

Abstract

Background 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. 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. Methods MTT, 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. Results AA 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. Conclusions Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.

Aspiletrein A Induces Apoptosis Cell Death via Increasing Reactive Oxygen Species Generation and AMPK Activation in Non-Small-Cell Lung Cancer Cells

“…In this study, we found that AA, a steroidal saponin from A. letreae , exhibited a potent apoptosis-inducing effect in NSCLC cells. Anticancer activities of AA have been previously reported [ 24 ], and this study also provides that AA has greater toxicity to the lung cancer cell lines than normal bronchial epithelial BEAS-2B cells, of which the selective index (SI) values were approximately 1.6–2.6-folds ( Table S1 ). Furthermore, we revealed the first evidence of the underlying molecular mechanism regarding the apoptosis-inducing effect.…”

“…Several anticancer drugs obtained from natural sources show versatile biological effects. Aspiletrein A (AA) is a steroidal saponin isolated from Aspidistra letreae [ 24 ] that exhibits various pharmacological activities, such as diuretic, expectorant, and antiviral and antifungal actions [ 25 ]. The cytotoxicity of this compound against several cancer types, including breast, cervical, lung, and gastric cancer cell lines, has also been reported [ 25 ].…”

“…The cytotoxicity of this compound against several cancer types, including breast, cervical, lung, and gastric cancer cell lines, has also been reported [ 25 ]. A recent study revealed that AA could attenuate lung cancer metastasis through suppression of the protein kinase B (Akt) signaling pathway and induced cell death by downregulation of the antiapoptotic Bcl-2 protein, whereas it has less toxicity to normal bronchial epithelial BEAS-2B cells [ 24 ]. However, the effect of AA treatment on apoptotic cell death and the interaction with AMPK have not yet been discovered.…”

Identifying molecular targets of Aspiletrein-derived steroidal saponins in lung cancer using network pharmacology and molecular docking-based assessments

“…For example, the plants of the Aspidistra genus, discovered in Vietnam 6 , contain many active components, such as saponin, coumarin, and isoflavones 7 , 8 , with various demonstrated pharmacological activities, including antibacterial, antifungal, antitumor, and antiviral 7 – 10 . A previous study reported that Aspiletreins, mainly three steroidal saponins, exhibited cytotoxicity in breast, cervical, hepatocellular, gastric, and lung cancer cells 8 , 11 . These three steroidal saponins contain different sugar moiety side chains located at C3, suggesting distinct potencies (Table 1 ).…”

“…These three steroidal saponins contain different sugar moiety side chains located at C3, suggesting distinct potencies (Table 1 ). The mechanistic investigation demonstrated that Aspiletrein A (AA) could suppress lung cancer metastasis by inhibiting protein kinase A (Akt) signaling 11 . However, the molecular targets of Aspiletreins B and C (AB and AC, respectively) have not been elucidated.…”