scholarly journals Structural basis for alpha fetoprotein‐mediated inhibition of caspase‐3 activity in hepatocellular carcinoma cells

2017 ◽  
Vol 141 (7) ◽  
pp. 1413-1421 ◽  
Author(s):  
Bo Lin ◽  
Mingyue Zhu ◽  
Wenting Wang ◽  
Wei Li ◽  
Xu Dong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Alpha Fetoprotein ◽  
Structural Basis ◽  
Hepatocellular Carcinoma Cells

scholarly journals Steroidal Saponins Isolated from the Rhizome of Dioscorea tokoro Inhibit Cell Growth and Autophagy in Hepatocellular Carcinoma Cells

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 749
Author(s):  
Shinya Okubo ◽  
Tomoe Ohta ◽  
Yukihiro Shoyama ◽  
Takuhiro Uto
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiproliferative Activity ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Parp Cleavage ◽  
Autophagic Flux ◽  
Steroidal Saponin ◽  
Steroidal Saponins ◽  
Active Compounds ◽  
Hepatocellular Carcinoma Cells

Our preliminary screening identified an extract from the rhizome of Dioscorea tokoro, which strongly suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. This study aimed to isolate active compounds from the rhizome of D. tokoro that exert antiproliferative effects and inhibit autophagy. The bioassay-guided fractionation of the active fraction led to the isolation of two spirostan-type steroidal saponins, dioscin (1) and yamogenin 3-O-α-l-rhamnopyranosyl (1→4)-O-α-l-rhamnopyranosyl(1→2)-β-d-glucopyranoside (2), and the frostane-type steroidal saponin protodioscin (3) from the n-BuOH fraction. Furthermore, acid hydrolysis of 1 and 2 produced the aglycones diosgenin (4) and yamogenin (5), respectively. Compounds 1–5 suppressed proliferation of HepG2 cells. The analysis of structure-activity relationships indicated that the 25(R)-conformation, structures with a sugar moiety, and the spirostan-type aglycone moiety contributed to antiproliferative activity. Analysis of autophagy-related proteins demonstrated that 1–3 clearly increased the levels of both LC3-II and p62, implying that 1–3 deregulate the autophagic pathway by blocking autophagic flux, which results in p62 and LC3-II accumulation. In contrast, 1–3 did not significantly affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative activity of 1–3 occurred independently of caspase-3-mediated apoptosis. In summary, our study showed that 1–3, active compounds in the rhizome of D. tokoro, suppressed cell proliferation and autophagy, and might be potential agents for autophagy research and cancer chemoprevention.

Effect of the BBC3 Gene on the Proliferation and Apoptosis of Hepatocellular Carcinoma Cells Through p53-Regulated Signaling

2021 ◽  
Vol 11 (1) ◽  
pp. 135-141
Author(s):  
Sheng Zheng ◽  
Hua Yang ◽  
Yefei Chang ◽  
Dan Zhao ◽  
Juan Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Hepg2 Cell ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Caspase 9 ◽  
Hepatocellular Carcinoma Cells ◽  
P53 Signaling ◽  
Normal Human Liver

We examined the effect of the BBC3 gene on hyperplasia and apoptosis in HepG2 cells and its underlying mechanism. Quantitative RT-PCR was used to determine the level of BBC3 expression in HL-7702 normal human liver cells and four different hepatocellular carcinoma cell lines (HepG2, HuH-7, HCCLM3 and MHCC97H). Transfection was performed with Lipofectamine 2000 reagent and the transfectants were divided into three groups: pcDNA-BBC3 group (transfected BBC3 over-expressing plasmid), pcDNA-NC group (transfected empty plasmid), and a Ctrl group (not transfected). Quantitative RT-PCR and western blot analysis were used to measure BBC3 expression. The CCK-8 assay was used to determine the effect of BBC3 on HepG2 cell proliferation. Flow cytometry was used for testing the effect of overexpressing BBC3 on apoptosis in HepG2 cells. The levels of cleaved-Caspase-3 (C-Caspase-3), cleaved-Caspase-9 (C-Caspase-9), and proteins associated with the p53 signaling pathway were assessed by western blot analysis. The level of BBC3 mRNA in HL-7702 normal human liver cells was significantly higher compared with that in human hepatocellular carcinoma cells including HepG2, HuH-7, HCCLM3 and MHCC97H (P < 0.05). The lowest level of BBC3 mRNA was observed in HepG2 cells. The level of BBC3 mRNA and protein in HepG2 cells were significantly higher compared with that of the pcDNA-NC group following transfection with a BBC3 overexpressing plasmid. HepG2 cell proliferation in the pcDNA-NC group was higher compared with that of the pcDNA-BBC3-transfected group (P < 0.05). The apoptotic rate and levels of cleaved-Caspase-3, cleaved-Caspase-9, p53, phospho-p53, and p21 protein in cells were higher compared with that of the pcDNA-NC group. No change was observed in the pcDNA-NC and Ctrl groups. The BBC3 gene was down-regulated in hepatocellular carcinoma cells. HepG2 cell proliferation can be inhibited and HepG2 cell apoptosis can be induced by the overexpression of BBC3 through activation of the p53 signaling pathway.

Artemisiae Iwayomogii Herba Inhibits Growth, Motility, and the PI3K/AKT/mTOR Signaling Pathway in Hepatocellular Carcinoma Cells

Planta Medica ◽  
2020 ◽  
Vol 86 (10) ◽  
pp. 717-727
Author(s):  
Juyoung Kim ◽  
Kyung Hee Jung ◽  
Jin Gyu Choi ◽  
Myung Sook Oh ◽  
Soon-Sun Hong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Caspase 3 ◽  
Carcinoma Cell ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Carcinoma Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mtor Signaling Pathway ◽  
Hepatocellular Carcinoma Cells ◽  
Hepatocellular Carcinoma Cell

Abstract Artemisia gmelinii (Artemisia iwayomogi) has been used in traditional medicine to cure various infectious diseases such as cholecystitis, hepatitis, and jaundice. In this study, the Artemisiae Iwayomogii Herba ethanol extract was investigated for the ability to inhibit growth of hepatocellular carcinoma and its underlying mechanism involved. The antiproliferative effect of Artemisiae Iwayomogii Herba ethanol extract was evaluated using cell viability and proliferation assays. The effect of Artemisiae Iwayomogii Herba ethanol extract on apoptosis was measured using western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling staining, JC-1 staining, cytochrome c release, immunohistochemistry, and immunofluorescence in ex vivo mouse xenografts. Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell growth and proliferation in a dose-dependent manner. The apoptotic effect of Artemisiae Iwayomogii Herba ethanol extract was observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling-positive apoptotic cells. Artemisiae Iwayomogii Herba ethanol extract also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell invasion and migration. In the ex vivo model, Artemisiae Iwayomogii Herba ethanol extract significantly inhibited tumor cell proliferation and increased the number of apoptotic cells with more activated cleaved caspase-3. A mechanistic study revealed that Artemisiae Iwayomogii Herba ethanol extract effectively suppressed the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma cells. Our findings demonstrate that Artemisiae Iwayomogii Herba ethanol extract can efficiently induce apoptosis and inhibit the growth, migration, and invasion of human hepatocellular carcinoma cells, and simultaneously block PI3K/AKT/mTOR pathway. We therefore suggest Artemisiae Iwayomogii Herba ethanol extract as a novel natural agent for prevention and therapy of hepatocellular carcinoma.

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