Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis through down-regulation of caspase-3 activity

Cancer ◽  
2004 ◽  
Vol 100 (11) ◽  
pp. 2430-2436 ◽  
Author(s):  
Tomoko Ohuchida ◽  
Kohji Okamoto ◽  
Kazuhisa Akahane ◽  
Aiichiro Higure ◽  
Hidekazu Todoroki ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
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.

scholarly journals DNA Damage Induces Down-Regulation of Prp19 via Impairing Prp19 Stability in Hepatocellular Carcinoma Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89976 ◽  
Author(s):  
Jie Yin ◽  
Yi-An Zhang ◽  
Tao-Tao Liu ◽  
Ji-Min Zhu ◽  
Xi-Zhong Shen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
Hepatocellular Carcinoma Cells

Selective Down-Regulation of Glioma-Associated Oncogene 2 Inhibits the Proliferation of Hepatocellular Carcinoma Cells

2007 ◽  
Vol 67 (8) ◽  
pp. 3583-3593 ◽  
Author(s):  
Youngsoo Kim ◽  
Joon Won Yoon ◽  
Xiaokun Xiao ◽  
Nicholas M. Dean ◽  
Brett P. Monia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
Hepatocellular Carcinoma Cells
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