Fucoxanthin Enhances Cisplatin-Induced Cytotoxicity  via NFκB-Mediated Pathway and Downregulates DNA Repair Gene Expression in Human Hepatoma HepG2 Cells

Liu, Cheng-Ling; Lim, Yun-Ping; Hu, Miao‐Lin

doi:10.3390/md11010050

Cited by 58 publications

(44 citation statements)

References 61 publications

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“…In our study, the ratio was increased indicating that exposure to these drugs can activate apoptosis cascade. The result is in line with several previous studies that showed that exposure of cells to 5-FU, CDDP and ET increased the ratio of BAX/BCL2 expression (Liu et al 2013;Sawada et al 2000;Singh et al 2006).…”

Section: Discussionsupporting

confidence: 94%

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Novak

Žegura

Baebler

et al. 2015

Environ Sci Pollut Res

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In chemotherapy, various anti-cancer drugs with different mechanisms of action are used and may represent different risk of undesirable delayed side effects in treated patients as well as in occupationally exposed populations. The aim of the present study was to evaluate genotoxic potential of four widely used anti-cancer drugs with different mechanisms of action: 5-fluorouracil (5-FU), cisplatin (CDDP) and etoposide (ET) that cause cell death by targeting DNA function and imatinib mesylate (IM) that inhibits targeted protein kinases in cancer cells in an experimental model with human hepatoma HepG2 cells. After 24 h of exposure all four anti-cancer drugs at non-cytotoxic concentrations induced significant increase in formation of DNA double strand breaks (DSBs), with IM being the least effective. The analysis of the changes in the expression of genes involved in the response to DNA damage (CDKN1A, GADD45A, MDM2), apoptosis (BAX, BCL2) and oncogenesis (MYC, JUN) showed that 5-FU, CDDP and ET upregulated the genes involved in DNA damage response, while the anti-apoptotic gene BCL2 and oncogene MYC were downregulated. On the contrary, IM did not change the mRNA level of the studied genes, showing different mechanism of action that probably does not involve direct interaction with DNA processing. Genotoxic effects of the tested anti-cancer drugs were observed at their therapeutic concentrations that may consequently lead to increased risk for development of delayed adverse effects in patients. In addition, considering the genotoxic mechanism of action of 5-FU, CDDP and ET an increased risk can also not be excluded in occupationally exposed populations. The results also indicate that exposure to 5-FU, CDDP and ET represent a higher risk for delayed effects such as cancer, reproductive effects and heritable disease than exposure to IM.

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Section: Discussionsupporting

confidence: 94%

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Novak

Žegura

Baebler

et al. 2015

Environ Sci Pollut Res

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“…The net result was inhibition of TP-mediated antiapoptosis leading to enhanced cisplatin cytotoxicity. Similar results were reported by another group using human hepatoma HepG2 cells [79]. Liu et al found that treating human hepatoma HepG2 cells with cisplatin alone led to increased TP expression through phosphorylation of ERK, p38 and PI3K/AKT pathways.…”

Section: Targeting Thymidine Phosphorylasesupporting

confidence: 88%

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Elamin

Rafee

Osman

et al. 2015

Cancer Microenvironment

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Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immuneresponse and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.

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“…The carotenoid fucoxanthin has been reported to inhibit NF-jB in HepG2 cells (Liu et al 2013). Sulphated polysaccharides such as fucoidan are known to possess immunomodulating as well as anti-inflammatory effects (Leiro et al 2007).…”

Section: Effect Of T Ornata and P Pavonia On Liver Nf-jb And Pparc mentioning

confidence: 99%

Brown seaweeds protect against azoxymethane-induced hepatic repercussions through up-regulation of peroxisome proliferator-activated receptor gamma and attenuation of oxidative stress

Abdella

Mahmoud

El-Derby

2016

Pharmaceutical Biology

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Objective: The current study determines the protective efficacy of the brown seaweeds Turbinaria ornata (Turner) J. Agardh (Sargassaceae) and Padina pavonia (Linnaeus) J.V. Lamouroux (Dictyotaceae) against liver injury induced by azoxymethane (AOM). Materials and methods: Male Swiss mice received 10 mg/kg AOM once a week for two consecutive weeks and then 100 mg/kg daily dose of either T. ornata or P. pavonia ethanolic extract. Thirteen weeks after the first AOM administration and 24 h after the last treatment, overnight fasted mice were sacrificed and samples collected. Results: Compared with the AOM group, both T. ornata and P. pavonia significantly decreased the activity of aminotransferases and the concentration of bilirubin while increased albumin levels in the serum. The antioxidative effect of both extracts was observed from the increased activity of superoxide dismutase and glutathione peroxidase activities in the liver, both of which were decreased by AOM. Moreover, the levels of malondialdehyde and nitric oxide were reduced, and histological findings also confirmed the antihepatotoxic activity. In addition, treatment with T. ornata and P. pavonia significantly increased PPARc and decreased NF-jB expression in the liver of AOM-administered mice. Discussion and conclusion: Our findings indicate that the protective function of T. ornata and P. pavonia on AOM-induced liver injury may be possibly exerted by multiple pathways including abolishment of inflammation and oxidative damage, and activation of PPARc. ARTICLE HISTORY

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Fucoxanthin Enhances Cisplatin-Induced Cytotoxicity via NFκB-Mediated Pathway and Downregulates DNA Repair Gene Expression in Human Hepatoma HepG2 Cells

Cited by 58 publications

References 61 publications

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Brown seaweeds protect against azoxymethane-induced hepatic repercussions through up-regulation of peroxisome proliferator-activated receptor gamma and attenuation of oxidative stress

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