15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells

Introduction. Ozone therapy is an effective medical treatment for different diseases like mucositis, psoriasis, acute pain, neurovascular diseases, and cancer. The aim of this study is based on the association of different ozone concentration with 5-fluorouracil and cisplatin in human colon cancer cell (HT29 cell line) in order to investigate possible anticancer synergistic effects. Methods. HT29 cells were incubated with ozone at different concentration ranging from 10 up to 50 μg/ml at different incubation time alone or in combination with cisplatin and 5-fluorouracil. Cell viability was performed by using a modified MTT method. Anti-inflammatory studies were conducted incubating HT29 with or without 20, 30, or 50 μg/ml of ozone before exposure to lipopolysaccharides. Results. Ozone alone has a time and concentration dependent cytotoxicity against HT29 cells (IC50 at 24 h: 30 μg/ml). Association of ozone with drugs increases cytotoxicity by 15–20%. Preincubation of ozone at 50 μg/ml decreases IL-8, IL-6, and IL-1β production by 50, 56, and 70%, respectively, compared to untreated cells. Conclusion. These results indicated that ozone could be useful in colon cancer management in combination with 5-fluorouracil and cisplatin with significant inhibition of cytokines having a central role in colon cancer cell survival and chemoresistance.

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Anti-Inflammatory Effect of Buckwheat Sprouts in Lipopolysaccharide-Activated Human Colon Cancer Cells and Mice

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.80324 ◽

2008 ◽

Vol 72 (12) ◽

pp. 3148-3157 ◽

Cited By ~ 30

Author(s):

Satoshi ISHII ◽

Takafumi KATSUMURA ◽

Chikara SHIOZUKA ◽

Keisuke OOYAUCHI ◽

Kunito KAWASAKI ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Anti Inflammatory ◽

Human Colon Cancer Cells ◽

Inflammatory Effect

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Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/423965 ◽

2013 ◽

Vol 2013 ◽

pp. 1-16 ◽

Cited By ~ 12

Author(s):

Kyeong-Ah Jung ◽

Mi-Kyoung Kwak

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Target Gene ◽

Human Colon ◽

Adduct Formation ◽

Mrna Levels ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Ht29 Cells ◽

Human Colon Cancer Cells

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.

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