Dataset Information

Application of Anti-Inflammatory Agents in Prostate Cancer.

ABSTRACT: Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular signaling molecules, such as cytokines and chemokines, thereby orchestrating the generation of inflammatory microenvironment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play pivotal roles in inflammation-associated cancer by inhibiting effective anti-tumor immunity. Anti-inflammatory agents, such as aspirin, metformin, and statins, have potential application in chemoprevention of prostate cancer. Furthermore, pro-inflammatory immunity-targeted therapies may provide novel strategies to treat patients with cancer. Thus, anti-inflammatory agents are expected to suppress the "vicious cycle" created by immune and cancer cells and inhibit cancer progression. This review has explored the immune cells that facilitate prostate cancer development and progression, with particular focus on the application of anti-inflammatory agents for both chemoprevention and therapeutic approach in prostate cancer.

SUBMITTER: Hatano K

PROVIDER: S-EPMC7464558 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Application of Anti-Inflammatory Agents in Prostate Cancer.

Hatano Koji K Fujita Kazutoshi K Nonomura Norio N

Journal of clinical medicine 20200818 8

Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular signaling molecules, such as cytokines and chemokines, thereby orchestrating the generation of inflammatory microenvironment. Tumor-associated macrophages (TAMs) and myeloid-deriv ...[more]

PMID: 32824865

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Project description:A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10, murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding that the most effective compound was compound 8c against all cell lines and both compounds 4 and 6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure because these products presented the lowest IC50 values in two of the three cancer cell lines assayed (B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line. Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing that the highest values were between 30 to 60%. Next, the effects of these two compounds were observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered by these compounds, mitochondrial potential was evaluated, indicating the possible activation of extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophages-monocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic concentrations were used to determine NO release at different incubation times. The greatest anti-inflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 µg·mL-1 concentration after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that inflammation may contribute to all states of tumorigenesis, the development of these new derivatives capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent new effective therapeutic strategies against these diseases.

Dataset Information

Application of Anti-Inflammatory Agents in Prostate Cancer.

Publications

Application of Anti-Inflammatory Agents in Prostate Cancer.

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