Kohei Mizuta, Ryosuke Mori, Qinghong Han, Sei Morinaga, Motokazu Sato, Byung Mo Kang, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman
{"title":"甲硫氨酸限制与多西他赛的结合能协同抑制雄激素依赖性前列腺癌，但不能抑制正常细胞。","authors":"Kohei Mizuta, Ryosuke Mori, Qinghong Han, Sei Morinaga, Motokazu Sato, Byung Mo Kang, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman","doi":"10.21873/cdp.10339","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and is a recalcitrant disease. Docetaxel is the first-line treatment for AIPC, but has limited efficacy and severe side-effects. All cancers are methionine-addicted, which is termed the Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of the present study was to determine if the combination of docetaxel and rMETase is effective for AIPC.</p><p><strong>Materials and methods: </strong>The half-maximal inhibitory concentrations (IC<sub>50</sub>) of docetaxel and rMETase alone were determined for the human AIPC cell line PC-3 and Hs27 normal human fibroblasts in vitro. The synergistic efficacy for PC-3 and Hs27 using the combination of docetaxel and rMETase at their IC<sub>50</sub>s for PC-3 was determined.</p><p><strong>Results: </strong>The IC<sub>50</sub> of docetaxel for PC-3 and for Hs27 was 0.72 nM and 0.94 nM, respectively. The IC<sub>50</sub> of rMETase for PC-3 and for Hs27 was 0.67 U/ml and 0.76 U/ml, respectively. The combination of docetaxel and rMETase was synergistic for PC-3 but not Hs27 cells.</p><p><strong>Conclusion: </strong>The combination of a relatively low concentration of docetaxel and rMETase was synergistic and effective for AIPC. The present results also suggest that the effective concentration of docetaxel can be reduced by using rMETase, which may reduce toxicity. The present results also suggest the future clinical potential of the combination of docetaxel and rMETase for AIPC.</p>","PeriodicalId":72510,"journal":{"name":"Cancer diagnosis & prognosis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215443/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Combination of Methionine Restriction and Docetaxel Synergistically Arrests Androgen-independent Prostate Cancer But Not Normal Cells.\",\"authors\":\"Kohei Mizuta, Ryosuke Mori, Qinghong Han, Sei Morinaga, Motokazu Sato, Byung Mo Kang, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman\",\"doi\":\"10.21873/cdp.10339\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and is a recalcitrant disease. Docetaxel is the first-line treatment for AIPC, but has limited efficacy and severe side-effects. All cancers are methionine-addicted, which is termed the Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of the present study was to determine if the combination of docetaxel and rMETase is effective for AIPC.</p><p><strong>Materials and methods: </strong>The half-maximal inhibitory concentrations (IC<sub>50</sub>) of docetaxel and rMETase alone were determined for the human AIPC cell line PC-3 and Hs27 normal human fibroblasts in vitro. The synergistic efficacy for PC-3 and Hs27 using the combination of docetaxel and rMETase at their IC<sub>50</sub>s for PC-3 was determined.</p><p><strong>Results: </strong>The IC<sub>50</sub> of docetaxel for PC-3 and for Hs27 was 0.72 nM and 0.94 nM, respectively. The IC<sub>50</sub> of rMETase for PC-3 and for Hs27 was 0.67 U/ml and 0.76 U/ml, respectively. The combination of docetaxel and rMETase was synergistic for PC-3 but not Hs27 cells.</p><p><strong>Conclusion: </strong>The combination of a relatively low concentration of docetaxel and rMETase was synergistic and effective for AIPC. The present results also suggest that the effective concentration of docetaxel can be reduced by using rMETase, which may reduce toxicity. The present results also suggest the future clinical potential of the combination of docetaxel and rMETase for AIPC.</p>\",\"PeriodicalId\":72510,\"journal\":{\"name\":\"Cancer diagnosis & prognosis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215443/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer diagnosis & prognosis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.21873/cdp.10339\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer diagnosis & prognosis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21873/cdp.10339","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
The Combination of Methionine Restriction and Docetaxel Synergistically Arrests Androgen-independent Prostate Cancer But Not Normal Cells.
Background/aim: Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and is a recalcitrant disease. Docetaxel is the first-line treatment for AIPC, but has limited efficacy and severe side-effects. All cancers are methionine-addicted, which is termed the Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of the present study was to determine if the combination of docetaxel and rMETase is effective for AIPC.
Materials and methods: The half-maximal inhibitory concentrations (IC50) of docetaxel and rMETase alone were determined for the human AIPC cell line PC-3 and Hs27 normal human fibroblasts in vitro. The synergistic efficacy for PC-3 and Hs27 using the combination of docetaxel and rMETase at their IC50s for PC-3 was determined.
Results: The IC50 of docetaxel for PC-3 and for Hs27 was 0.72 nM and 0.94 nM, respectively. The IC50 of rMETase for PC-3 and for Hs27 was 0.67 U/ml and 0.76 U/ml, respectively. The combination of docetaxel and rMETase was synergistic for PC-3 but not Hs27 cells.
Conclusion: The combination of a relatively low concentration of docetaxel and rMETase was synergistic and effective for AIPC. The present results also suggest that the effective concentration of docetaxel can be reduced by using rMETase, which may reduce toxicity. The present results also suggest the future clinical potential of the combination of docetaxel and rMETase for AIPC.
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