scholarly journals Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1627
Author(s):  
Min Yeong Kim ◽  
Hyesook Lee ◽  
Seon Yeong Ji ◽  
So Young Kim ◽  
Hyun Hwangbo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Human Hepatocellular Carcinoma ◽  
Multicellular Tumor Spheroid ◽  
Jnk Signaling ◽  
Anti Cancer ◽  
Jnk Signaling Pathway ◽  
Hep3b Cells ◽  
Induction Of Apoptosis ◽  
Cancer Activity

Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to investigate the anti-proliferative effects of IALT in human hepatocellular carcinoma (HCC) cells and to evaluate the potential anti-cancer mechanisms. Our results demonstrated that IALT treatment concentration-dependently suppressed the cell survival of HCC Hep3B cells, which was associated with the induction of apoptosis. IALT increased the expression of death-receptor-related proteins, activated caspases, and induced Bid truncation, subsequently leading to cleavage of poly (ADP-ribose) polymerase. In addition, IALT contributed to the cytosolic release of cytochrome c by destroying mitochondrial integrity, following an increase in the Bax/Bcl-2 expression ratio. However, IALT-mediated growth inhibition and apoptosis were significantly attenuated in the presence of a pan-caspase inhibitor, suggesting that IALT induced caspase-dependent apoptosis in Hep3B cells. Moreover, IALT activated the mitogen-activated protein kinases signaling pathway, and the anti-cancer effect of IALT was significantly diminished in the presence of a potent c-Jun N-terminal kinase (JNK) inhibitor. IALT also improved the generation of intracellular reactive oxygen species (ROS), whereas the ROS inhibitor significantly abrogated IALT-induced growth reduction, apoptosis, and JNK activation. Furthermore, ROS-dependent apoptosis was revealed as a mechanism involved in the anti-cancer activity of IALT in a 3D multicellular tumor spheroid model of Hep3B cells. Taken together, our findings indicate that IALT exhibited anti-cancer activity in HCC Hep3B cells by inducing ROS-dependent activation of the JNK signaling pathway.

scholarly journals Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

2020 ◽  
Vol 21 (15) ◽  
pp. 5502 ◽  
Author(s):  
So Young Kim ◽  
Hyun Hwangbo ◽  
Hyesook Lee ◽  
Cheol Park ◽  
Gi-Young Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Apoptotic Cell ◽  
Death Receptor ◽  
Jnk Signaling ◽  
Anticancer Efficacy ◽  
Bax Protein ◽  
Diagnosis Rate ◽  
Jnk Signaling Pathway ◽  
Hep3b Cells

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome c into the cytoplasm. However, N-acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.

scholarly journals Vitexin suppresses autophagy to induce apoptosis in hepatocellular carcinoma via activation of the JNK signaling pathway

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 84520-84532 ◽  
Author(s):  
Jin-Dan He ◽  
Zhen Wang ◽  
Shi-Peng Li ◽  
Yan-Jie Xu ◽  
Yao Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

scholarly journals Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chengshuo Zhang ◽  
Jialin Zhang ◽  
Xin Li ◽  
Ning Sun ◽  
Rui Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Aqueous Extract ◽  
Cell Apoptosis ◽  
S Phase ◽  
Carcinoma Cells ◽  
Jnk Signaling ◽  
Hepatocellular Carcinoma Cells ◽  
Jnk Signaling Pathway

Huaier aqueous extract, the main active constituent of Huaier proteoglycan, has antihepatocarcinoma activity in experimental and clinical settings. However, the potential and associated antihepatoma mechanisms of Huaier extract are not yet fully understood. Therefore, in this study, we aimed to elucidate the inhibitory proliferation effect of Huaier extract on apoptosis and cycle of HepG2 and Bel-7402 cells. Our data demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability dose-dependently. Flow cytometric analysis showed that a 48 h treatment of Huaier extract caused cell apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after Hoechst staining. Immunoblot analysis further demonstrated that Huaier extract activated caspase 3 and PARP. Additionally, Huaier extract inhibited the activity of p-ERK, p-p38, and p-JNK in terms of MAPK. Furthermore, Huaier extract induced HCC cells arrest in S phase and decreased the cycle related protein expression ofβ-catenin and cyclin D1. Studies with JNK specific inhibitor, SP600125, showed that Huaier extract induced S phase arrest and decreasedβ-catenin and cyclin D1 expression via JNK signaling pathway. In conclusion, we verify that Huaier extract causes cell apoptosis and induces hepatocellular carcinoma cells arrest in S phase via JNK pathway, which advances our understanding on the molecular mechanisms of Huaier extract in hepatocarcinoma management.

scholarly journals URM1 Promoted Tumor Growth and Suppressed Apoptosis via the JNK Signaling Pathway in Hepatocellular Carcinoma

2020 ◽  
Vol Volume 13 ◽  
pp. 8011-8025
Author(s):  
Xin Cheng ◽  
Yu Zhang ◽  
Fei Song ◽  
Fengliang Song ◽  
Cheng Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

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.

scholarly journals A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 12831-12842 ◽  
Author(s):  
Xiaoyun Dai ◽  
Lingzhi Wang ◽  
Amudha Deivasigamni ◽  
Chung Yeng Looi ◽  
Chandrabose Karthikeyan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Benzimidazole Derivative ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway
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