Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways

Shao, Linjun; Hu, Lihua; Yan, Sheng; Jin, Jianmin; Ren, Shao‐Yan

doi:10.3892/ol.2016.4706

Cited by 53 publications

(33 citation statements)

References 36 publications

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“…Taken together, these data suggest that MRE could induce apoptosis of Hep3B cells through mitochondria- and Fas-mediated caspase-dependent pathways. These mechanisms have been reported previously using different agents to induce apoptosis of HCC cells [67–69]. …”

Section: Discussionsupporting

confidence: 72%

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

Alwahibi

Khalil

Ibrahim

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes. MRE treatment induced apoptotic effects to HepG2 cells in a caspase-dependent manner and via upregulating p53/p21 and PCNA. The upregulation of p21 was controlled by p53 expression in HepG2 but not in Hep3B despite upregulation of Bax protein in both cell lines. Interestingly, p21 may be a remarkable switch to G1 arrest in HepG2 cells, but not in Hep3B cells. In addition, Fas- and mitochondria-mediated pathways were found to be involved in MRE-induced apoptosis in Hep3B cells. The GC-MS analysis of MRE revealed two major constituents of pharmaceutical importance: the flavonoid apigenin (17.04%) and the terpenoid squalene (11.32%). The data presented in this paper introduces G. bruguieri as a promising nontoxic herb with therapeutic potential for HCC. To the authors' knowledge, the present study provides the first report on the anticancer activity of MRE on HCC cells.

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Section: Discussionsupporting

confidence: 72%

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

Alwahibi

Khalil

Ibrahim

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…It is know that changes in mitochondrial membrane permeability can cause the mitochondria mediated apoptosis signal pathway start [33,34]. However, our results showed that fluoride did not induce mitochondrial swelling of hepatocytes.…”

Section: Discussioncontrasting

confidence: 65%

Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure

Campos-Pereira

Lopes‐Aguiar

Renosto

et al. 2017

Chemico-Biological Interactions

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Studies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress. Semi-quantitative RT-PCR and immunostaining to determine mRNA and protein expression of antioxidant enzymes. Analyses of the hepatic function and morphology were performed. Our results revealed the genotoxic potential of fluoride but did not confirm mitochondrial swelling nor an increase of positive TUNEL labelling induced by fluoride, indicating absence of apoptosis. Oxidative stress induction was confirmed and is probably associated to DNA damage. Cell death events such as empty nuclear spaces, cytoplasm degeneration, nuclear pyknosis, karyorrhexis and karyorrhexis followed by karyolysis were observed. Hepatic function did not appear to be significantly modified makes no evidence of necrosis and suggesting other cell death pathway, the autophagic. In conclusion, prolonged fluoride intake at chosen concentrations caused imbalance of the cellular oxidative state, affected DNA and disrupted cellular homeostasis. It is recommended that fluoride supplementation requires a fresh consideration in light of the current study.

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“…Activation of multiple death receptors or the withdrawal of cytokines induces extrinsic pathway-mediated apoptosis [14,15]. Both the intrinsic and extrinsic pathways lead to the release of cytochrome C and other apoptosis-inducing factors, which subsequently activate downstream caspases [16]. …”

Section: Introductionmentioning

confidence: 99%

Differential Impacts of Alternative Splicing Networks on Apoptosis

Lin

Tsao

Lin

2016

IJMS

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Apoptosis functions as a common mechanism to eliminate unnecessary or damaged cells during cell renewal and tissue development in multicellular organisms. More than 200 proteins constitute complex networks involved in apoptotic regulation. Imbalanced expressions of apoptosis-related factors frequently lead to malignant diseases. The biological functions of several apoptotic factors are manipulated through alternative splicing mechanisms which expand gene diversity by generating discrete variants from one messenger RNA precursor. It is widely observed that alternatively-spliced variants encoded from apoptosis-related genes exhibit differential effects on apoptotic regulation. Alternative splicing events are meticulously regulated by the interplay between trans-splicing factors and cis-responsive elements surrounding the regulated exons. The major focus of this review is to highlight recent studies that illustrate the influences of alternative splicing networks on apoptotic regulation which participates in diverse cellular processes and diseases.

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Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways

Cited by 53 publications

References 36 publications

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure

Differential Impacts of Alternative Splicing Networks on Apoptosis

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