Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway

Abstract

AIMTo explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway.METHODSThe experiments were conducted on three groups: an experimental group (with ST ethanol extracts’ concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes.RESULTSCompared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased (P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased (P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.CONCLUSIONST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway.

Ethanol Extracts of Solanum lyratum Thunb Regulate Ovarian Cancer Cell Proliferation, Apoptosis, and Epithelial-to-Mesenchymal Transition (EMT) via the ROS-Mediated p53 Pathway

“…Our results suggested that SLT plays an important role in inhibiting ovarian tumor progression. Previous study reported that the extract of SLT can inhibit the growth of SMMC-7721 cells and induce apoptosis through the mitochondrial pathway in hepatocellular carcinoma [ 25 ]. In human colon adenocarcinoma cells, SLT induced cell cytotoxicity and apoptosis, and regulated the expression of CDK1, p27, p53, cyclin B1, cyclin E, caspase-3, caspase-8, caspase-9, Bcl-2, Bax, and cytochrome C activity [ 18 ].…”

Phytochemical and pharmacological studies on Solanum lyratum: a review

“…The heat-clearing and detoxicating property of S. lyratum is favorable in the treatment of cancer [ 17 , 19 , 21 ]. It has been reported that S. lyratum treats various cancers by inhibiting the tumor growth [ 74 , 75 ], enhancing immunity [ 76 , 78 ] and inducing apoptosis via activating both extrinsic and intrinsic apoptotic pathways [ 27 , 34 , 79 ].…”

“…Total alkaloids from S. lyratum (SLTA, 24 mL/kg) could inhibit the tumor growth in mice with Lewis lung cancer, and when combined with cisplatin, a synergistic effect had been shown to down-regulate the mRNA expression of Notch1, Notch3 and Jagged1 in Notch signaling pathway [ 81 ]. In addition, the hexane fraction of the methanol extract (50 mg/kg) of S. lyratum showed similar inhibitory activity on tumor growth in mice with Lewis lung carcinoma tumor, potentially acting through up-regulating Fas, caspase-8, caspase-3, and p53, and down-regulating FasL and B-cell lymphoma-2 (Bcl-2) in the mitochondrial pathway [ 27 , 79 ].…”

Picrasma quassioides Extract Elevates the Cervical Cancer Cell Apoptosis Through ROS-Mitochondrial Axis Activated p38 MAPK Signaling Pathway

“…JC-1 is a membrane permeable dye that selectively enters the mitochondria and can detect the intracellular mitochondrial membrane potential. When the mitochondrial membrane potential is high, JC-1 accumulates inside the mitochondria forming aggregates, which can generate red fluorescence; when the mitochondrial membrane potential is low, JC-1 cannot be gathered in the matrix of the mitochondria, it remains a monomer and produces green fluorescence (28). The results showed that the ratio of green fluorescence (low ∆Ψm) to red fluorescence (high ∆Ψm) of JC-1 in SiHa cells was significantly increased in various concentrations (0, 40, 60 μg/ml) of PQ treatment ( Figure 2C).…”