Solasonine, the main active ingredient of Solanum nigrum L., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) in vitro. Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia in vitro and in vivo and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.

Context: ShengMaBieJia decoction (SMBJD) is used to treat solid and hematological tumours; however, its anti-angiogenesis activity remains unclear.Objective: This study verified the anti-angiogenic effects of SMBJD in vitro and in tumour-bearing acute myeloid leukaemia (AML) mouse models. Materials and methods: In vivo, the chicken chorioallantoic membrane (CAM) and BALB/c null mouse xenograft models were treated with SMBJD (0, 2, 4, and 8 mg/mL) for 48 h and for 2 weeks, respectively. Anti-angiogenic activity was assessed according to microvessel density (MVD) and immunohistochemistry (IHC) targeting CD31 and VEGFR2. In vitro, proliferation viability, migratory activity and tube formation were measured. Western blots and polymerase chain reaction (PCR) assays were used to examine the levels of PI3K, Akt, and VEGF. Results: HPLC analyses revealed the active constituents of SMBJD such as liquiritin, cimifugin, ferulic, isoferulic, and glycyrrhizic acids. In vitro, SMBJD treatment decreased cellular migration, chemotaxis, and tube formation at non-cytotoxic concentrations (2, 4, and 8 mg/mL) in a time-and dose-dependent manner. The dosage of less than IC 20 is considered safe. In vivo, CAM models exhibited a decrease in MVD, and the tissues of xenografted mice possessed reduced CD31 and VEGFR2 expression. Conditioned media (CM) from AML cells (HL60 and NB4 cells) treated with non-cytotoxic doses of SMBJD inhibited chemotactic migration and tube formation in vitro. Both CM (HL60) and CM (NB4) exhibited downregulated expression of PI3K, Akt, and VEGF. Discussion and conclusions: SMBJD inhibited angiogenesis in AML through the PI3K/AKT pathway, which might be combined with targeted therapy to provide more effective treatment.

Shengma Biejia decoction (SMBJD), a traditional Chinese formula recorded in the Golden Chamber, has been widely used for the treatment of malignant tumors. However, its underlying molecular targets and mechanisms are still unclear. This study showed that SMBJD inhibited tumor growth and stimulated hemogram recovery significantly in a multiple myeloma xenograft model. Western blot and immunohistochemistry assays of tumor tissues showed that SMBJD reduced the ratio of autophagy-related proteins LC3-II/LC3-I, while P62 and apoptosis-related proteins cleaved caspase-3/caspase-3 and Bax/Bcl-2 were upregulated. In vitro experiments demonstrated the time-dependent and dose-dependent cytotoxicity of SMBJD on multiple myeloma cell lines H929 and U266 through MTT assays. The LC3-II/LC3-I ratio and number of GFP-LC3 puncta showed that SMBJD inhibited the autophagy process of H929 and U266 cells. Moreover, both SMBJD and 3-methyladenine (3-MA) caused a decrease in LC3-II/LC3-I, and SMBJD could not reverse the upregulation of LC3-II/LC3-I caused by bafilomycin A1 (Baf-A1). Furthermore, the results of annexin V-FITC and propidium iodide double staining demonstrated that SMBJD treatment induced the apoptosis of H929 and U266 cells. These data prove that SMBJD inhibits autophagy and promotes apoptosis in H929 and U266 cells. The results also show that rapamycin could reduce the rate of SMBJD-induced apoptosis in H929 and U266 cells, at a concentration which had no effect on apoptosis but activated autophagy. In addition, analysis of the mechanism indicated that levels of phosphorylated ERK and phosphorylated mTOR were increased by treatment with SMBJD in vivo and in vitro. These results indicate that SMBJD, an old and effective herbal compound, could inhibit the viability of H929 and U266 cells and induce autophagy-mediated apoptosis through the ERK/mTOR pathway. Thus, it represents a potential therapy strategy for multiple myeloma.