Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells

Malik, Durr-e-shahwar; David, Rachel; Gooderham, Nigel J.

doi:10.1007/s00204-018-2291-z

Cited by 41 publications

(26 citation statements)

References 66 publications

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“…Given that the inflammatory response has been reported to modulate GC development [32–34] and that BaP is a carcinogen that is most likely ingested during daily human life [35, 36], BaP can induce cancerous lesions in the human stomach and result in gastric carcinogenesis by promoting a pro-inflammatory phenotype [5, 37–39]. In addition, feeding of mice with BaP has been an extensively applied method for the establishment of mouse GC models [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice

et al. 2019

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Background Chronic gastritis has been demonstrated to be a key cause of gastric cancer (GC), and control of gastric inflammation is regarded as an effective treatment for the clinical prevention of gastric carcinogenesis. However, there remains an unmet need to identify the dominant regulators of gastric oncogenesis-associated inflammation in vivo. Methods The mouse model for the study of inflammation-associated GC was induced by Benzo[a]pyrene (BaP) intragastric administration in Bcl6b −/− and wildtype mice on a C57BL/6 background. 5-Aza-2′-deoxycytidine (5-Aza), the demethylation drug, was intraperitoneally injected to restore Bcl6b expression. Human GC tissue array was used to analyse patient survival based on BCL6B and CD3 protein expression. Results Bcl6b was gradually downregulated by its own promoter hypermethylation in parallel to an increasing inflammatory response during the progression of BaP-induced gastric carcinogenesis in mice. Moreover, knockout of Bcl6b dramatically worsened the severity of gastric cancer and aggravated the inflammatory response in the BaP-induced mice GC model. Re-activation of Bcl6b by 5-Aza impeded inflammatory amplification and BaP-induced GC development, prolonging survival time in wildtype mice, whereas no notable curative effect occurred in Bcl6b −/− mice with 5-Aza treatment. Finally, significant negative correlations were detected between the mRNA levels of BCL6B and inflammatory cytokines in human GC tissues; patients harbouring BCL6B-negetive and severe-inflammation GC tumours were found to exhibit the shortest survival time. Conclusions Epigenetic inactivation of Bcl6b promotes gastric cancer through amplification of the gastric inflammatory response in vivo and offers a new approach for GC treatment and regenerative medicine. Electronic supplementary material The online version of this article (10.1186/s12964-019-0387-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice

et al. 2019

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“…Benzo[a]pyrene, a constituent of CS, has been shown to promote inflammation pathways via TNF - α and NF - κB , leading to IL - 6 upregulation, miRNA ( let - 7a , miR - 21 and miR - 29b ) dysregulation and the activation of VEGF [195]. The downregulation of let - 7a and miR - 29b and the upregulation of miR - 21 induced by benzo[a]pyrene in human mammary cells were associated with the altered expression of inflammation mediators.…”

Section: Epigenetics and Inflammationmentioning

confidence: 99%

The role of cigarette smoke-induced epigenetic alterations in inflammation

Zong

Liu

et al. 2019

Epigenetics & Chromatin

122

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Background: Exposure to cigarette smoke (CS) is a major threat to human health worldwide. It is well established that smoking increases the risk of respiratory diseases, cardiovascular diseases and different forms of cancer, including lung, liver, and colon. CS-triggered inflammation is considered to play a central role in various pathologies by a mechanism that stimulates the release of pro-inflammatory cytokines. During this process, epigenetic alterations are known to play important roles in the specificity and duration of gene transcription. Main text: Epigenetic alterations include three major modifications: DNA modifications via methylation; various posttranslational modifications of histones, namely, methylation, acetylation, phosphorylation, and ubiquitination; and non-coding RNA sequences. These modifications work in concert to regulate gene transcription in a heritable fashion. The enzymes that regulate these epigenetic modifications can be activated by smoking, which further mediates the expression of multiple inflammatory genes. In this review, we summarize the current knowledge on the epigenetic alterations triggered by CS and assess how such alterations may affect smoking-mediated inflammatory responses. Conclusion: The recognition of the molecular mechanisms of the epigenetic changes in abnormal inflammation is expected to contribute to the understanding of the pathophysiology of CS-related diseases such that novel epigenetic therapies may be identified in the near future.

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“…Kamel et al (2012) states that TNF-α is the most widely expressed inflammatory cytokine in breast cancer. Likewise, according to Malik et al (2018) TNFα has been shown to increase breast cancer cell growth. The number of cells expressing TNF-α in mammary carcinoma has been known to be related to tumor grade and plays a role in metastasis in mammary carcinoma.…”

Section: Discussionmentioning

confidence: 99%

High-Fat Diet Decreases Serum TNF-Alpha and Breast Tumor Area on Benzopyrene Induced Mice (Mus Musculus)

Rejeki¹,

Utami²,

Izzatunnisa³

et al. 2021

CMUJNS

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This study aims to analyze whether the high-fat diet decreases serum TNF-α and breast tumor area on benzopyrene induced mice (Mus musculus). This study was a true experimental with the randomized posttest-only control group design using 36 female mice (Mus musculus), 3-4 months age, 25 ± 5 grams. Mice were induced with benzopyrene (BZP) subcutaneously with a dose of 0.3mg/20gBB/day for 14 days in the right breast area, then randomly divided into 6 groups, K1 (negative control group, given standard feed), K2 (positive control group, standard feed), K3 (high-fat diet with a ratio of 60% protein, 0% carbohydrate, 30% fat, 10% fiber), K4 (high-fat diet with a ratio of 45% protein, 0% carbohydrate, 45% fat, 10% fiber), K5 (high-fat diet with a ratio of 30% protein, 0% carbohydrate, 60% fat, 10% fiber) and K6 (high-fat diet on day 15 with a ratio of 15% protein, 0% carbohydrate, 75% fat, 10% fiber). The high-fat diet was administered for 28 days. The mean of tumor area delta at K1 (0.00 ± 0.00) mm2, K2 (3.52 ± 1.98) mm2, K3 (27.18 ± 21.23) mm2, K4 (13.19 ± 9.93) mm2, K5 (8.80 ± 1.72) mm2, K6 (10.81 ± 6.55) mm2, and (p=0.001). The mean of TNF-α levels at K1 (56.32 ± 8.25) ng/mL, K2 (65.99 ± 2.82) ng/mL, K3 (70.43 ± 4.61) ng/mL, K4 (58.05 ± 5.80) ng/mL, K5 (54.91 ± 3.27) ng/mL, K6 (59.67 ± 3.63) ng/mL and (P = 0.000). A high-fat diet lowers TNF-α levels and reduces the area of BZP-induced breast tumors. The lowest TNF-α levels and the lowest breast tumor area were found in groups with a fat: protein ratio = 60:30. Keywords: Benzopyrene induced, Breast tumor area, High-fat diet, Tumor necrosis factor-α

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Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells

Cited by 41 publications

References 66 publications

Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice

Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice

The role of cigarette smoke-induced epigenetic alterations in inflammation

High-Fat Diet Decreases Serum TNF-Alpha and Breast Tumor Area on Benzopyrene Induced Mice (Mus Musculus)

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