{"title":"姜黄素与内源性大麻素再摄取抑制剂OMDM-2在人MCF-7乳腺癌和U-87胶质母细胞瘤细胞中协同作用","authors":"R.M. Ammar , G. Ulrich-Merzenich","doi":"10.1016/j.synres.2017.11.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Δ<sup>9</sup>-Tetrahydrocannabinol (THC), active constituent of <em>Cannabis sativa</em> L., possesses potential antitumor activity. Modulating the endogenous level of cannabinoids could be a sensible strategy to avoid adverse events presently limiting the use of direct agonists. We investigated the cytotoxicity of endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with the polyphenol curcumin, an active compound of <em>Curcuma longa</em> L.</p></div><div><h3>Methods</h3><p>The <em>in-vitro</em> anti-proliferative activities of OMDM-2 alone/in combination with curcumin were evaluated in breast cancer (MCF-7) and glioblastoma (U-87) cells using the resazurin assay. The effect of curcumin on OMDM-2 was determined by comparing different inhibitory concentrations (IC) values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by the combination index (CI) and isobologram analyses.</p></div><div><h3>Results</h3><p>OMDM-2 by itself showed anti-proliferative effects against both MCF-7 and U-87 cells in a dose dependent manner with IC<sub>50</sub> values of 4.9<!--> <!-->μM and 2.7<!--> <!-->μM respectively. Isobol and CI analyses at different dose ratios revealed that the drug interaction was predominantly synergistic against MCF-7 cells (CI<!--> <!-->≤<!--> <!-->0.5 at IC<sub>50</sub>). While in case of glioblastoma cells CI values varied between <0.2 up to 1.1 at IC<sub>70</sub> depending on the ratio and concentration of the drugs.</p></div><div><h3>Conclusion</h3><p>These findings provide experimental support for the use of curcumin as a modulator of tumor cell pharmacointeraction in cannabinoid based therapies. To achieve synergism dose ratios should be established for each cell type and ratiometric dosing be considered.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2017.11.001","citationCount":"2","resultStr":"{\"title\":\"Curcumin synergizes with the endocannabinoid reuptake inhibitor OMDM-2 in human MCF-7 breast cancer and U-87 glioblastoma cells\",\"authors\":\"R.M. Ammar , G. Ulrich-Merzenich\",\"doi\":\"10.1016/j.synres.2017.11.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Δ<sup>9</sup>-Tetrahydrocannabinol (THC), active constituent of <em>Cannabis sativa</em> L., possesses potential antitumor activity. Modulating the endogenous level of cannabinoids could be a sensible strategy to avoid adverse events presently limiting the use of direct agonists. We investigated the cytotoxicity of endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with the polyphenol curcumin, an active compound of <em>Curcuma longa</em> L.</p></div><div><h3>Methods</h3><p>The <em>in-vitro</em> anti-proliferative activities of OMDM-2 alone/in combination with curcumin were evaluated in breast cancer (MCF-7) and glioblastoma (U-87) cells using the resazurin assay. The effect of curcumin on OMDM-2 was determined by comparing different inhibitory concentrations (IC) values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by the combination index (CI) and isobologram analyses.</p></div><div><h3>Results</h3><p>OMDM-2 by itself showed anti-proliferative effects against both MCF-7 and U-87 cells in a dose dependent manner with IC<sub>50</sub> values of 4.9<!--> <!-->μM and 2.7<!--> <!-->μM respectively. Isobol and CI analyses at different dose ratios revealed that the drug interaction was predominantly synergistic against MCF-7 cells (CI<!--> <!-->≤<!--> <!-->0.5 at IC<sub>50</sub>). While in case of glioblastoma cells CI values varied between <0.2 up to 1.1 at IC<sub>70</sub> depending on the ratio and concentration of the drugs.</p></div><div><h3>Conclusion</h3><p>These findings provide experimental support for the use of curcumin as a modulator of tumor cell pharmacointeraction in cannabinoid based therapies. To achieve synergism dose ratios should be established for each cell type and ratiometric dosing be considered.</p></div>\",\"PeriodicalId\":38079,\"journal\":{\"name\":\"Synergy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.synres.2017.11.001\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Synergy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213713017300330\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synergy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213713017300330","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Curcumin synergizes with the endocannabinoid reuptake inhibitor OMDM-2 in human MCF-7 breast cancer and U-87 glioblastoma cells
Introduction
Δ9-Tetrahydrocannabinol (THC), active constituent of Cannabis sativa L., possesses potential antitumor activity. Modulating the endogenous level of cannabinoids could be a sensible strategy to avoid adverse events presently limiting the use of direct agonists. We investigated the cytotoxicity of endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with the polyphenol curcumin, an active compound of Curcuma longa L.
Methods
The in-vitro anti-proliferative activities of OMDM-2 alone/in combination with curcumin were evaluated in breast cancer (MCF-7) and glioblastoma (U-87) cells using the resazurin assay. The effect of curcumin on OMDM-2 was determined by comparing different inhibitory concentrations (IC) values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by the combination index (CI) and isobologram analyses.
Results
OMDM-2 by itself showed anti-proliferative effects against both MCF-7 and U-87 cells in a dose dependent manner with IC50 values of 4.9 μM and 2.7 μM respectively. Isobol and CI analyses at different dose ratios revealed that the drug interaction was predominantly synergistic against MCF-7 cells (CI ≤ 0.5 at IC50). While in case of glioblastoma cells CI values varied between <0.2 up to 1.1 at IC70 depending on the ratio and concentration of the drugs.
Conclusion
These findings provide experimental support for the use of curcumin as a modulator of tumor cell pharmacointeraction in cannabinoid based therapies. To achieve synergism dose ratios should be established for each cell type and ratiometric dosing be considered.