High O6-methylguanine methyl transferase activity is frequently found in human oral cancer cells with p53 inactivation.

Guo, Weiwen; Liu, Xuan; Lee, S.; Park, N.-H.

doi:10.3892/ijo.15.4.817

Cited by 3 publications

(3 citation statements)

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“…EGCG also suppresses signal transduction cascades that lead to AP1 factor activation (6,44) and decreases c-Jun phosphorylation in transformed and immortalized human bronchial epithelial cell lines (45).…”

Section: Discussionmentioning

confidence: 99%

Green Tea Polyphenol Stimulates a Ras, MEKK1, MEK3, and p38 Cascade to Increase Activator Protein 1 Factor-dependent Involucrin Gene Expression in Normal Human Keratinocytes

Balasubramanian¹,

Efimova²,

Eckert³

2002

Journal of Biological Chemistry

133

138

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(؊)-Epigallocatechin-3-gallate (EGCG) is an important bioactive constituent of green tea that efficiently reduces epidermal cancer cell proliferation. This inhibition is associated with a reduction in activator protein 1 (AP1) transcription factor level and activity. However, its effects on AP1 function in normal epidermal cells have not been extensively explored. Our present studies show that EGCG regulates normal keratinocyte function. To understand the mechanism of action, we examined the effects of EGCG on AP1 factor activity, MAPK signal transduction, and expression of the AP1 factorregulated human involucrin (hINV) gene. EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP1 factor binding to hINV promoter AP1 site. Gel mobility shift studies show that this complex contains Fra-1 and JunD. Signal transduction analysis indicates that the EGCG response requires Ras, MEKK1, MEK3, and p38 kinases. Kinase assays and inhibitor studies suggest that p38␦ is the p38 isoform responsible for the regulation. These changes are also associated with a cessation of cell proliferation and enhanced cornified envelope formation. These studies show that in normal human keratinocytes EGCG markedly increases, via a MAPK signaling mechanism, AP1 factor-associated responses.The polyphenol constituents of green tea inhibit carcinogenesis in a variety of tissues (1-4); however, their mechanism of action is not well understood. (Ϫ)-Epigallocatechin-3-gallate (EGCG) 1 is the major polyphenol isolated from green tea. AP1 transcription factors and AP1 factor-associated signal transduction are important targets of EGCG action (5-7). AP1 proteins consist of homodimers of Jun proteins (c-Jun, JunB, and JunD) and heterodimers of Jun and Fos (c-Fos, FosB, Fra-1, and Fra-2) factors (8). These proteins regulate transcription, differentiation, and cell proliferation by binding to specific recognition motifs in target genes (9 -13). EGCG produces specific changes in AP1 factor function in immortalized and transformed keratinocytes. These changes include an EGCGdependent reduction in phorbol ester-dependent mitogen-activated protein kinase (MAPK) activity (6), and reduced AP1 factor level and activity (7,14). EGCG also inhibits ultraviolet light-associated activation of c-Fos gene expression and the accumulation of c-Fos protein (7). Based on these studies, it has been suggested that the cancer-preventive role of EGCG may be due, in part, to its ability to reduce AP1 factor-related responses (6,7,14). However, very little information is available regarding how EGCG effects AP1 factor-regulated responses in normal keratinocytes. Our present studies show that EGCG increases AP1 factor levels in normal keratinocytes, and increases human involucrin gene expressio...

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Section: Discussionmentioning

confidence: 99%

Green Tea Polyphenol Stimulates a Ras, MEKK1, MEK3, and p38 Cascade to Increase Activator Protein 1 Factor-dependent Involucrin Gene Expression in Normal Human Keratinocytes

Balasubramanian¹,

Efimova²,

Eckert³

2002

Journal of Biological Chemistry

133

138

View full text Add to dashboard Cite

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“…Potential reasons for the observed decrease in DNA adducts while the amount of CYP1B1 protein still increases could be an induction of detoxifying enzymes, such as glutathione S-transferases, DNA repair, or-as shown in experiments with human CYP1B1 microsomes-a competitive inhibition of CYP1B1 activity by B[a]P or its metabolites such as diol [64][65][66]. In lung cells and other cellular models, non-tumorigenic cells are more sensitive relative to tumorigenic cells, which acquire characteristics that make them more resistant to stress factors and prone to grow uncontrolled [67][68][69]. For example, increased DNA repair is known to occur in tumorigenic cells that survive chemotherapy and radiation therapy [67]; in A549 cells compared the BEAS-2B cells, the DNA repair machinery for non-homologous end joining is increased in response to nickel exposure [69].…”

Section: Discussionmentioning

confidence: 99%

“…In lung cells and other cellular models, non-tumorigenic cells are more sensitive relative to tumorigenic cells, which acquire characteristics that make them more resistant to stress factors and prone to grow uncontrolled [67][68][69]. For example, increased DNA repair is known to occur in tumorigenic cells that survive chemotherapy and radiation therapy [67]; in A549 cells compared the BEAS-2B cells, the DNA repair machinery for non-homologous end joining is increased in response to nickel exposure [69].…”

Section: Discussionmentioning

confidence: 99%

The Carcinogenic Properties of Overlooked yet Prevalent Polycyclic Aromatic Hydrocarbons in Human Lung Epithelial Cells

Bauer

Siegrist

Wolff

et al. 2022

Toxics

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The WHO classified air pollution as a human lung carcinogen and polycyclic aromatic hydrocarbons (PAHs) are components of both indoor (e.g., tobacco smoke and cookstoves) and outdoor (e.g., wildfires and industrial and vehicle emissions) air pollution, thus a human health concern. However, few studies have evaluated the adverse effects of low molecular weight (LMW) PAHs, the most abundant PAHs in the environment. We hypothesized that LMW PAHs combined with the carcinogenic PAH benzo[a]pyrene (B[a]P) act as co-carcinogens in human lung epithelial cell lines (BEAS-2B and A549). Therefore, in this paper, we evaluate several endpoints, such as micronuclei, gap junctional intercellular communication (GJIC) activity, cell cycle analysis, anti-BPDE-DNA adduct formation, and cytotoxicity after mixed exposures of LMW PAHs with B[a]P. The individual PAH doses used for each endpoint did not elicit cytotoxicity nor cell death and were relevant to human exposures. The addition of a binary mixture of LMW PAHs (fluoranthene and 1-methylanthracene) to B[a]P treated cells resulted in significant increases in micronuclei formation, dysregulation of GJIC, and changes in cell cycle as compared to cells treated with either B[a]P or the binary mixture alone. In addition, anti-BPDE-DNA adducts were significantly increased in human lung cells treated with B[a]P combined with the binary mixture of LMW PAHs as compared to cells treated with B[a]P alone, further supporting the increased co-carcinogenic potential by LMW PAHs. Collectively, these novel studies using LMW PAHs provide evidence of adverse pulmonary effects that should warrant further investigation.

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Diversity and implication of MAPK signal transduction involved in the regulation of chemotherapy-induced DNA damage response

Alaoui‐Jamali

Wurzba

Bijian

2016

DNA Repair in Cancer Therapy

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High O6-methylguanine methyl transferase activity is frequently found in human oral cancer cells with p53 inactivation.

Cited by 3 publications

References 0 publications

Green Tea Polyphenol Stimulates a Ras, MEKK1, MEK3, and p38 Cascade to Increase Activator Protein 1 Factor-dependent Involucrin Gene Expression in Normal Human Keratinocytes

Green Tea Polyphenol Stimulates a Ras, MEKK1, MEK3, and p38 Cascade to Increase Activator Protein 1 Factor-dependent Involucrin Gene Expression in Normal Human Keratinocytes

The Carcinogenic Properties of Overlooked yet Prevalent Polycyclic Aromatic Hydrocarbons in Human Lung Epithelial Cells

Diversity and implication of MAPK signal transduction involved in the regulation of chemotherapy-induced DNA damage response

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