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.

scholarly journals Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769141 ◽  
Author(s):  
Qing Gou ◽  
ShuJiao He ◽  
ZeJian Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Small Interfering Rna ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Carcinoma Cell Lines ◽  
Hepatocellular Carcinoma Cell ◽  
Interfering Rna ◽  
Methyltransferase 1

Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

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 Notoamide-type alkaloid induced apoptosis and autophagyviaa P38/JNK signaling pathway in hepatocellular carcinoma cells

RSC Advances ◽  
2019 ◽  
Vol 9 (34) ◽  
pp. 19855-19868 ◽  
Author(s):  
Likun Hu ◽  
Ting Zhang ◽  
Dong Liu ◽  
Guiwen Guan ◽  
Jian Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Aspergillus Ochraceus ◽  
Jnk Signaling ◽  
Carcinoma Cell Lines ◽  
Jnk Signaling Pathway ◽  
Hepatocellular Carcinoma Cell ◽  
Induced Apoptosis

Eleven notoamides including four new congeners were isolated fromAspergillus ochraceus. Notoamide G inhibited the viability of hepatocellular carcinoma cell lines by regulation of apoptosis and autophagy through P38/JNK signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document