Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro

Boehme, Kathleen; Dietz, Yasmin; Hewitt, Philip; Mueller, Stefan O.

doi:10.1016/j.toxlet.2010.07.007

Cited by 29 publications

(17 citation statements)

References 64 publications

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“…In disagreement with our result and although curcumin is a powerful inhibitor of tumor cell proliferation, however, it induced growth arrest and apoptosis of B cell lymphoma and human melanoma cells by downregulating p53 (p53-independent mechanism) [41]. As reported previously, HepG2 cells exhibit a wild-type inducible p53 activity [42], which in turn may explain the involvement of the upregulation of p53 in the MRE-induced apoptosis in HepG2 cells.…”

Section: Discussioncontrasting

confidence: 89%

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: Discussioncontrasting

confidence: 89%

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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“…In principle, it may be an indication that the activity of CYPs are involved in the toxicity of CYN at very low concentrations, even though cells may recover from CYN insult at 48 h of exposure. Phenobarbital has proved to be a very effective CYP inducer in HepG2 in other studies (Boehme et al 2010;Turpeinen et al, 2009;Walter and Willem, 2007), particularly for isoforms CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5 (Fig. 2).…”

Section: Cyps Induction Can Make Hepg2 Cells More Sensitive To Cyn Tomentioning

confidence: 83%

“…In addition, CYPs-induction impaired the effects of CYN on cell proliferation and so may have important consequences concerning tumor cells. Tumor cells usually express low levels of xenobiotic-metabolizing enzymes (Boehme et al, 2010;Liu and Zeng, 2009;Matsuda et al, 2002) in comparison to normal cells, so that CYN can favor proliferation of these cells. Only a few published studies have reported CYN influence on the cell cycle and proliferation.…”

Section: Low Concentrations Of Cyn Induce Hepg2 Cells Proliferation Amentioning

confidence: 99%

“…In particular, HepG2 cells retain the activity of many phase I and II enzymes, although at lower levels than fresh isolated human adult hepatocytes (Rueff et al, 1996;Walter and Willem, 2007) also described to NADPHcytochrome P450 reductase and cytochrome b5 (Rodríguez-antona et al, 2002;Yoshitomi et al, 2001). Because of this some authors have suggested the need of cells stimulation with nuclear receptors (AhR, PXR and CAR) activators (Westerink and Schoonen, 2007a,b) or treatment with selective CYP inducers such as b-naphtoflavone, rifampin, phenobarbital and ethanol (Boehme et al, 2010;Liu and Zeng, 2009;Matsuda et al, 2002) before cytotoxicity tests.…”

Section: Introductionmentioning

confidence: 99%

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Low concentrations of cylindrospermopsin induce increases of reactive oxygen species levels, metabolism and proliferation in human hepatoma cells (HepG2)

Liebel

Ribeiro

Magalhães

et al. 2015

Toxicology in Vitro

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“…In this study, HepG2 cell was used as a test system, due to its inherent capacity of enzymes for metabolism, and also this cell expresses the p53 protein, which is useful to screen p53 mediated DNA damage (Boehme et al 2010, Zager et al 2010). …”

Section: Introductionmentioning

confidence: 99%

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

Muthusamy¹

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Mixed contamination of polyaromatic hydrocarbons (PAHs) and metals are ubiquitous in the environment. Some of the individual PAHs are known as human carcinogens, and metals are associated with various systemic toxicity and cancers in humans. Although the individual toxicity of PAHs and metals are well documented, our present state of knowledge about the adverse health effects of these mixtures is very limited in terms of exposure associated toxicity in humans, the underlying mechanism of toxicity and predicting the toxicity of mixtures. Due to this, their risk assessment has been mostly carried out based on their individual toxicity data.This research work investigated the interaction and combined toxicity of four PAHs

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Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro

Cited by 29 publications

References 64 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

Low concentrations of cylindrospermopsin induce increases of reactive oxygen species levels, metabolism and proliferation in human hepatoma cells (HepG2)

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

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