scholarly journals Anticarcinogenic effect of indole-3-carbinol (I3C) on human hepatocellular carcinoma SNU449 cells

2018 ◽  
Vol 38 (1) ◽  
pp. 136-147 ◽  
Author(s):  
CM Lee ◽  
S-H Park ◽  
MJ Nam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Human Hepatocellular Carcinoma ◽  
Time Dependent ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Caspase 7 ◽  
Thioredoxin 1 ◽  
Induced Apoptosis ◽  
Apoptotic Effects

Many cruciferous vegetables, including cabbage, contain indole-3-carbinol (I3C), which is a known anticarcinogen. However, the anticarcinogenic effects of I3C on liver cancer have not been investigated. Therefore, this study was conducted to evaluate the anticarcinogenic effects of I3C in human hepatocellular carcinoma (HCC) SNU449 cells. The results of MTT and WST-1 assays indicated that treatment of SNU449 cells with I3C decreased viability in dose- and time-dependent manners, while colony formation assays indicated that I3C also inhibited proliferation of SNU449 cells. Moreover, fluorescence-activated cell sorter analysis showed that I3C induced apoptosis in SNU449 cells in dose- and time-dependent manners. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling revealed that I3C induced DNA fragmentation in SNU449 cells in a time-dependent manner, while Western blotting showed that apoptotic proteins such as p53, cleaved PARP, caspase-3, and caspase-7 were activated in SNU449 cells following treatment with I3C. Finally, reactive oxygen species-related protein peroxiredoxin-1 and thioredoxin-1 expression decreased in I3C-treated SNU449 cells. The aim of our study is to investigate the unknown mechanisms responsible for the apoptotic effects of I3C on human HCC SNU449 cells, and the results suggest that I3C may be useful for the prevention and treatment of liver cancer.

scholarly journals Antiproliferative and Apoptotic Effects of Cardamonin against Hepatocellular Carcinoma HepG2 Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1757
Author(s):  
Nassrin A. Badroon ◽  
Nazia Abdul Majid ◽  
Mohammed A. Alshawsh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Primary Liver Cancer ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Major Health Problem ◽  
Major Health ◽  
Late Apoptosis ◽  
Apoptotic Effects

Liver cancer is the sixth most common cancer in terms of incidence and the fourth in terms of mortality. Hepatocellular carcinoma (HCC) represents almost 90% of primary liver cancer and has become a major health problem globally. Cardamonin (CADMN) is a natural bioactive chalcone found in several edible plants such as cardamom and Alpinia species. Previous studies have shown that CADMN possesses anticancer activities against breast, lung, prostate and colorectal cancer. In the present study, the mechanisms underlying the anti-hepatocellular carcinoma effects of CADMN were investigated against HepG2 cells. The results demonstrated that CADMN has anti-proliferative effects and apoptotic action on HepG2 cells. CADMN showed potent cytotoxicity against HepG2 cells with an IC50 of 17.1 ± 0.592 μM at 72 h. Flow cytometry analysis demonstrated that CADMN arrests HepG2 cells in G1 phase and induces a significant increase in early and late apoptosis in a time-dependent manner. The mechanism by which CADMN induces apoptotic action was via activation of both extrinsic and intrinsic pathways. Moreover, the findings of this study showed the involvement of reactive oxygen species (ROS), which inhibit the NF-κB pathway and further enhance the apoptotic process. Together, our findings further support the potential anticancer activity of CADMN as an alternative therapeutic agent against HCC.

scholarly journals NeosedumosideIII induced Apoptosis of Human Hepatocellular Carcinoma HepG2 cells and SMMC-7721 Cells and Related Mechanism

2021 ◽  
Author(s):  
Xin-Yu Li ◽  
Xin Zhou ◽  
Yu- Liu ◽  
Feng Qiu ◽  
Qing-Qing Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Induced Apoptosis

Abstract Purpose: NeosedumosideIII (Neo) is a megastigmanes and belongs to monocyclic sesquiterpenoids compound with antioxidant, anti-inflammatory and other pharmacological activities. In order to explore the anti-cancer effect and possible mechanism of Neo, the study examined the anti-proliferation and apoptosis effect of Neo against human hepatocellular carcinoma HepG2 cells and SMMC-772 cells and related mechanism in vitro. Methods ：The anti-proliferation effect of Neo was detected on HepG2 cells and SMMC-772 cells by MTT assay and IC50 with increasing dose and time. Cell cycle and apoptosis were detected by flow cytometer. The changes of Bcl-2, Bax, Caspase-3, Caspase-8 and Caspase-9 proteins were detected by western blotting.Results ：The results indicated that Neo could inhibited proliferation of HepG2 cells and SMMC-772 cells in vitro and promoted apoptosis, it significantly induced apoptosis of HepG2 cells and SMMC-772 cells arrested cell cycle at G0/G1 phase in a dose-dependent manner, reduce the expression of Bcl-2 protein, and increase the expression of Bax and Caspase-3, Caspase-8 and Caspase-9 proteins. Conclusion：Neo could inhibit proliferation and induce apoptosis of HepG2 cells and SMMC-7721 cells in vivo which suggested that it might be served as a promising candidate for the treatment of liver cancer.

Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Erianin Involves a Mitochondria-Mediated Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 261-269
Author(s):  
Zhong Min ◽  
He Lei ◽  
Shi Yujie ◽  
Chen Xin ◽  
Ren Jianwu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Activity ◽  
Hepg2 Cells ◽  
Chinese Herb ◽  
Human Hepatocellular Carcinoma ◽  
Dependent Manner ◽  
M Cell ◽  
Cytochrome C Release ◽  
Intracellular Ca ◽  
Induced Apoptosis

Erianin is a natural product derived from the traditional Chinese herb, Dendrobium chrysotoxum, which is highly valued for its antitumor activity in various cancer cells. However, the specific mechanism of antitumor activity of erianin in human hepatocellular carcinoma remains unclear. This study aimed to investigate erianin-induced apoptosis in human hepatocellular carcinoma HepG2 cells. The proliferation of HepG2 cells was significantly inhibited by the treatment of erianin in a doseand time-dependent manner. In addition, erianin induced a series of apoptosis-related events in HepG2 cells, including G2/M cell cycle arrest, the loss of the mitochondrial membrane potential, elevation of intracellular Ca2+, and accumulation of reactive oxygen species. Erianin activated the caspase-3 and caspase-9 without a change in caspase-8, accompanied by upregulation of the expression of Bax and downregulation of the expression of Bcl-2 along with cytochrome C release from the mitochondria. There was no significant change in Fas and FasL expression, indicating that the exogenous pathway is not involved in erianin-induced apoptosis. In summary, it concluded that erianin-induced apoptosis in HepG2 cells is through a mitochondria-mediated pathway. The results of this study suggest that erianin may serve as a novel therapeutic agent for the treatment of human hepatocellular carcinoma in the future.

scholarly journals Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

2019 ◽  
pp. 10-16
Author(s):  
Mohammed Y. Alhassani ◽  
Samir F. Zohny ◽  
Ryan A. Sheikh ◽  
Mohammed A. Hassan ◽  
Abdulaziz A. Kalantan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Nigella Sativa ◽  
Human Hepatocellular Carcinoma ◽  
Biologically Active ◽  
New Drugs ◽  
Pcr Analysis ◽  
Dependent Manner

Human hepatocellular carcinoma (HCC) is the most prevalent and recurrent type of primary adult liver cancer without any effective therapy. Thus, there is an increase demands for finding new drugs and treatment strategies with selective and potent effects towards HCC. Plant-derived compounds acting as anti-cancer agents can induce apoptosis through targeting several signaling pathways. Thymoquinone (TQ), the major biologically active compound of the black seed oil (Nigella sativa) has demonstrated inhibitory activities on various cancers by targeting several pathways. In the present study, we have evaluated the molecular mechanisms that underlie the anti-proliferative, anti-metastatic, and pro-apoptotic activities exerted by TQ on liver cancer cell lineHepG2, a well-documented HCC in vitro model. Cell proliferation was determined by WST-1 assay, apoptosis rate was assessed by flow cytometry using annexin-V/7AAD staining, wound healing assay to investigate the metastasis, and the expression of target genes was assessed by Real-time RT–PCR analysis. We found that TQ significantly reduced HepG2 cell viability and induced apoptosis in a dose-dependent manner. Migration of HepG2 cells was suppressed in response to TQ. Moreover, TQ decreased the expression of several angiogenesis-related genes including versican (VCAN), growth factor receptor-bound protein 2 (Grb2), and the histone methyltransferase for lysine 27 of histone 3 (EZH2). The findings suggest that TQ exerts inhibitory effects on HCC most likely through targeting key genes involved in the invasiveness and

scholarly journals Indole-3-Carbinol Induces Apoptosis in Human Osteosarcoma MG-63 and U2OS Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Chang Min Lee ◽  
Jongsung Lee ◽  
Myeong Jin Nam ◽  
See-Hyoung Park
Keyword(s):  
Cell Sorting ◽  
Caspase 3 ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Facs Analysis ◽  
Caspase 9 ◽  
Human Osteosarcoma ◽  
Caspase 7 ◽  
U2os Cells ◽  
Induced Apoptosis

This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against osteosarcoma MG-63 and U2OS cells. A wound healing assay indicated that IC3 inhibited migration of MG-63 and U2OS cells. MTT, WST-1, and colony formation assays revealed that treatment of MG-63 and U2OS cells with I3C decreased cell viability. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced apoptosis in a dose- and time-dependent manner in MG-63 and U2OS cells. Moreover, via terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP-biotin nick-end labeling (TUNEL) assay, we detected that I3C induced DNA fragmentation. Western blotting demonstrated that activated forms of caspase-3, caspase-7, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP) were increased in MG-63 and U2OS cells, following treatment with I3C. Furthermore, protein expression levels of FOXO3, Bax, and Bim extra-large form were increased while those of Akt, JNK, p38, phosphorylated ERK, and Bcl-xL were decreased by I3C treatment in MG-63 and U2OS cells. Thus, the study indicates that I3C may induce apoptosis in human osteosarcoma MG-63 and U2OS cells via the activation of apoptotic signaling pathways by FOXO3.

scholarly journals SLC6A8 Knockdown Suppresses the Invasion and Migration of Human Hepatocellular Carcinoma Huh-7 and Hep3B Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382098302
Author(s):  
Lu Yuan ◽  
Xian Jian Wu ◽  
Wen Chuan Li ◽  
Chenyi Zhuo ◽  
ZuoMing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vital Role ◽  
Human Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Solute Carrier Family ◽  
Invasion And Migration ◽  
Behavioral Abnormalities ◽  
Solute Carrier ◽  
Induced Apoptosis

Liver cancer is considered the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide. Currently, there is no specific and effective therapy for hepatocellular carcinoma. Therefore, developing novel diagnostic and therapeutic strategies against hepatocellular carcinoma is of paramount importance. Solute carrier family 6 member 8 (SLC6A8) encodes the solute carrier family 6-8 to transport creatine into cells in a Na+ and Cl-- dependent manner. SLC6A8 deficiency is characterized by intellectual disabilities, loss of speech, and behavioral abnormalities. Of concern, the association of SLC6A8 with hepatocellular carcinoma remains elusive. In this study, we revealed that SLC6A8 knockdown significantly induced apoptosis and suppressed the migration and invasion of Hep3B and Huh-7 cells. These findings depicted the vital role of SLC6A8 in the initiation and progression of human hepatocellular carcinoma.

scholarly journals Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Juyoung Kim ◽  
Kyung Hee Jung ◽  
Hyung Won Ryu ◽  
Doo-Young Kim ◽  
Sei-Ryang Oh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Caspase 3 ◽  
Mtor Pathway ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Xanthium Strumarium ◽  
Apoptotic Effects ◽  
Hcc Cells

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were 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- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

Induction of apoptosis by particulate matter: role of TNF-α and MAPK

1998 ◽  
Vol 275 (5) ◽  
pp. L942-L949 ◽  
Author(s):  
Beek Yoke Chin ◽  
Mary E. Choi ◽  
Marie D. Burdick ◽  
Robert M. Strieter ◽  
Terence H. Risby ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Carbon Black ◽  
Mapk Pathway ◽  
Time Dependent ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Mapk Kinase ◽  
Tnf Α ◽  
Induced Apoptosis

Particulate matter (PM) is a major by-product from the combustion of fossil fuels. The biological target of inhaled PM is the pulmonary epithelium and resident macrophages. In this study, we demonstrate that cultured macrophages (RAW 264.7 cells) exposed continously to a well-defined model of PM [benzo[ a]pyrene adsorbed on carbon black (CB+BaP)] exhibit a time-dependent expression and release of the cytokine tumor necrosis factor-α (TNF-α). CB+BaP also evoked programmed cell death or apoptosis in cultured macrophages as assessed by genomic DNA-laddering assays. The CB+BaP-induced apoptosis was inhibited when macrophages were treated with CB+BaP in the presence of a neutralizing antibody to TNF-α, suggesting that TNF-α plays an important role in mediating CB+BaP-induced apoptosis in macrophages. Interestingly, neither untreated carbon black nor benzo[ a]pyrene alone induced apoptosis or caused the release of TNF-α in RAW 264.7 cells. Moreover, we observed that TNF-α activates mitogen-activated protein kinase (MAPK) activity, the extracellular signal-regulated kinases p42/p44, in a time-dependent manner. RAW 264.7 cells treated with PD-098059, a selective inhibitor of MAPK kinase activity, did not exhibit CB+BaP-induced apoptosis and TNF-α secretion. Furthermore, cells treated with the MAPK kinase inhibitor did not undergo TNF-α-induced apoptosis. Taken together, our data suggest that TNF-α mediates PM-induced apoptosis and that the MAPK pathway may play an important role in regulating this pathway.

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