{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:04:13Z","timestamp":1775819053157,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s11033-026-11768-0","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:07:14Z","timestamp":1775815634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel recombinant arginine deiminase from Limosilactobacillus reuteri DSM 20016 demonstrates anticancer activity against colon cancer cells"],"prefix":"10.1007","volume":"53","author":[{"given":"Darshali Pravin","family":"Thakker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Gor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrasudan","family":"Ramamurthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satish","family":"Ramalingam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajnish","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"11768_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209\u2013249","journal-title":"CA Cancer J Clin"},{"key":"11768_CR2","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229\u2013263","journal-title":"CA Cancer J Clin"},{"key":"11768_CR3","first-page":"394","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394\u2013424","journal-title":"CA Cancer J Clin"},{"key":"11768_CR4","first-page":"7","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72:7\u201333","journal-title":"CA Cancer J Clin"},{"key":"11768_CR5","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1002\/ijc.25202","volume":"126","author":"B Delage","year":"2010","unstructured":"Delage B, Fennell DA, Nicholson L et al (2010) Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer 126:2762\u20132772","journal-title":"Int J Cancer"},{"key":"11768_CR6","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1097\/00001813-200410000-00002","volume":"15","author":"DN Wheatley","year":"2004","unstructured":"Wheatley DN (2004) Controlling cancer by restricting arginine availability\u2013arginine-catabolizing enzymes as anticancer agents. Anticancer Drugs 15:825\u2013833","journal-title":"Anticancer Drugs"},{"key":"11768_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2025.118367","volume":"130","author":"L Dai","year":"2025","unstructured":"Dai L, Wen S, Chen Y et al (2025) Self-assembled dual-target ibuprofen-irinotecan conjugate for colorectal cancer therapy. Bioorg Med Chem 130:118367","journal-title":"Bioorg Med Chem"},{"issue":"Pt 1","key":"11768_CR8","first-page":"1","volume":"336","author":"G Wu","year":"1998","unstructured":"Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1\u201317","journal-title":"Biochem J"},{"key":"11768_CR9","first-page":"5443","volume":"62","author":"CM Ensor","year":"2002","unstructured":"Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA (2002) Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res 62:5443\u20135450","journal-title":"Cancer Res"},{"key":"11768_CR10","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/cncr.20057","volume":"100","author":"BJ Dillon","year":"2004","unstructured":"Dillon BJ, Prieto VG, Curley SA et al (2004) Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer 100:826\u2013833","journal-title":"Cancer"},{"key":"11768_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004761","volume":"7","author":"F Qiu","year":"2014","unstructured":"Qiu F, Chen Y-R, Liu X et al (2014) Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells. Sci Signal 7:ra31","journal-title":"Sci Signal"},{"key":"11768_CR12","doi-asserted-by":"publisher","first-page":"102257","DOI":"10.1016\/j.genrep.2025.102257","volume":"40","author":"P Darshali","year":"2025","unstructured":"Darshali P, Thakker RN (2025) Molecular cloning and enzymatic characterization of arginine deiminase (LrADI) from Limosilactobacillus reuteri DSM 20016: A candidate for cancer metabolic therapy. Gene Rep 40:102257","journal-title":"Gene Rep"},{"key":"11768_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-9-9","volume":"9","author":"S-M Tsui","year":"2009","unstructured":"Tsui S-M, Lam W-M, Lam T-L et al (2009) Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC). Cancer Cell Int 9:9","journal-title":"Cancer Cell Int"},{"key":"11768_CR14","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.2174\/138161208784246199","volume":"14","author":"L Feun","year":"2008","unstructured":"Feun L, You M, Wu CJ et al (2008) Arginine deprivation as a targeted therapy for cancer. Curr Pharm Des 14:1049\u20131057","journal-title":"Curr Pharm Des"},{"key":"11768_CR15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s00284-009-9376-0","volume":"58","author":"Y Ni","year":"2009","unstructured":"Ni Y, Li Z, Sun Z et al (2009) Expression of arginine deiminase from Pseudomonas plecoglossicida CGMCC2039 in Escherichia coli and its anti-tumor activity. Curr Microbiol 58:593\u2013598","journal-title":"Curr Microbiol"},{"key":"11768_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-020-02212-6","volume":"10","author":"K Bala","year":"2020","unstructured":"Bala K, Husain I, Sharma A (2020) Arginine deaminase from PS2: purification, biochemical characterization and in-vitro evaluation of anticancer activity. 3 Biotech 10:226","journal-title":"3 Biotech"},{"key":"11768_CR17","first-page":"5443","volume":"62","author":"CM Ensor","year":"2002","unstructured":"Ensor CM (2002) Pegylated arginine deiminase (ADI-SS-PEG 20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res 62:5443\u20135450","journal-title":"Cancer Res"},{"key":"11768_CR18","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1158\/1078-0432.CCR-18-3729","volume":"25","author":"PE Hall","year":"2019","unstructured":"Hall PE (2019) A phase I study of pegylated arginine deiminase (ADI-PEG20) in patients with advanced solid tumors. Clin Cancer Res 25:2708\u20132716","journal-title":"Clin Cancer Res"},{"key":"11768_CR19","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamaoncol.2016.3049","volume":"3","author":"PW Szlosarek","year":"2017","unstructured":"Szlosarek PW, Steele JP, Nolan L et al (2017) Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1\u2013deficient malignant pleural mesothelioma. JAMA Oncol 3:58","journal-title":"JAMA Oncol"},{"key":"11768_CR20","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1200\/JCO.2013.49.8691","volume":"31","author":"PA Ascierto","year":"2013","unstructured":"Ascierto PA, Minor D, Ribas A et al (2013) Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 31:3205\u20133211","journal-title":"J Clin Oncol"},{"key":"11768_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1195-4","volume":"9","author":"JM Przystal","year":"2018","unstructured":"Przystal JM, Hajji N, Khozoie C et al (2018) Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM. Cell Death Dis 9:1192","journal-title":"Cell Death Dis"},{"key":"11768_CR22","unstructured":"Riss TL, Moravec RA, Niles AL et al (2016) Cell viability assays. Assay guidance manual"},{"key":"11768_CR23","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.3390\/ijms23084073","volume":"23","author":"C-H Hwang","year":"2022","unstructured":"Hwang C-H, Lee N-K, Paik H-D (2022) The anti-cancer potential of heat-killed Lactobacillus brevis KU15176 upon AGS cell lines through intrinsic apoptosis pathway. Int J Mol Sci 23:4073","journal-title":"Int J Mol Sci"},{"key":"11768_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/toxics11080669","volume":"11","author":"R Gor","year":"2023","unstructured":"Gor R, Gharib A, Dharshini Balaji P et al (2023) Inducing cytotoxicity in colon cancer cells and suppressing cancer stem cells by dolasetron and ketoprofen through inhibition of RNA binding protein PUM1. Toxics 11:669","journal-title":"Toxics"},{"key":"11768_CR25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/cbf.3135","volume":"33","author":"M Pagano","year":"2015","unstructured":"Pagano M, Faggio C (2015) The use of erythrocyte fragility to assess xenobiotic cytotoxicity. Cell Biochem Funct 33:351\u2013355","journal-title":"Cell Biochem Funct"},{"key":"11768_CR26","doi-asserted-by":"publisher","first-page":"25518","DOI":"10.1038\/srep25518","volume":"6","author":"H Huang","year":"2016","unstructured":"Huang H, Lai W, Cui M et al (2016) An evaluation of blood compatibility of silver nanoparticles. Sci Rep 6:25518","journal-title":"Sci Rep"},{"key":"11768_CR27","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1038\/nprot.2006.339","volume":"1","author":"NAP Franken","year":"2006","unstructured":"Franken NAP, Rodermond HM, Stap J et al (2006) Clonogenic assay of cells in vitro. Nat Protoc 1:2315\u20132319","journal-title":"Nat Protoc"},{"key":"11768_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.399","volume":"4","author":"S Kumar","year":"2013","unstructured":"Kumar S, Guru SK, Pathania AS et al (2013) Autophagy triggered by magnolol derivative negatively regulates angiogenesis. Cell Death Dis 4:e889","journal-title":"Cell Death Dis"},{"key":"11768_CR29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cbi.2017.07.001","volume":"274","author":"I Husain","year":"2017","unstructured":"Husain I, Bala K, Wani A et al (2017) Arginase purified from endophytic Pseudomonas aeruginosa IH2: Induce apoptosis through both cell cycle arrest and MMP loss in human leukemic HL-60 cells. Chem Biol Interact 274:35\u201349","journal-title":"Chem Biol Interact"},{"key":"11768_CR30","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot087205","volume":"2016","author":"LC Crowley","year":"2016","unstructured":"Crowley LC, Marfell BJ, Waterhouse NJ (2016) Analyzing Cell Death by Nuclear Staining with Hoechst 33342. Cold Spring Harb Protoc 2016:pdb.prot087205. https:\/\/doi.org\/10.1101\/pdb.prot087205","journal-title":"Cold Spring Harb Protoc"},{"key":"11768_CR31","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-022-01851-4","volume":"39","author":"R Gor","year":"2022","unstructured":"Gor R, Saha L, Agarwal S et al (2022) Morin inhibits colon cancer stem cells by inhibiting PUM1 expression in vitro. Med Oncol 39:251","journal-title":"Med Oncol"},{"key":"11768_CR32","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3390\/cells13131141","volume":"13","author":"B Dukic","year":"2024","unstructured":"Dukic B, Ruppert Z, T\u00f3th ME et al (2024) Mild hyperthermia-induced thermogenesis in the endoplasmic reticulum defines stress response mechanisms. Cells 13:1141","journal-title":"Cells"},{"key":"11768_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30591-7","volume":"8","author":"C Alexandrou","year":"2018","unstructured":"Alexandrou C, Al-Aqbi SS, Higgins JA et al (2018) Sensitivity of colorectal cancer to arginine deprivation therapy is shaped by differential expression of urea cycle enzymes. Sci Rep 8:12096","journal-title":"Sci Rep"},{"key":"11768_CR34","doi-asserted-by":"publisher","first-page":"405","DOI":"10.2174\/156652410791316995","volume":"10","author":"N Savaraj","year":"2010","unstructured":"Savaraj N, You M, Wu C et al (2010) Arginine deprivation, autophagy, apoptosis (AAA) for the treatment of melanoma. Curr Mol Med 10:405\u2013412","journal-title":"Curr Mol Med"},{"key":"11768_CR35","first-page":"5443","volume":"62","author":"CM Ensor","year":"2002","unstructured":"Ensor CM (2002) Pegylated arginine deiminase (ADI-PEG20): a novel antitumor enzyme. Cancer Res 62:5443\u20135450","journal-title":"Cancer Res"},{"key":"11768_CR36","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ctrv.2011.12.008","volume":"38","author":"LG Feun","year":"2012","unstructured":"Feun LG (2012) Arginine deprivation in cancer therapy: ADI-PEG20 and beyond. Cancer Treat Rev 38:484\u2013491","journal-title":"Cancer Treat Rev"},{"key":"11768_CR37","doi-asserted-by":"crossref","unstructured":"Morris SM Jr (2007) Arginine metabolism: boundaries of our knowledge. J Nutr 137:1602S-1609S","DOI":"10.1093\/jn\/137.6.1602S"},{"key":"11768_CR38","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0022-1759(02)00072-8","volume":"265","author":"H Lecoeur","year":"2002","unstructured":"Lecoeur H, de Oliveira-Pinto LM, Gougeon M-L (2002) Multiparametric flow cytometric analysis of biochemical and functional events associated with apoptosis and oncosis using the 7-aminoactinomycin D assay. J Immunol Methods 265:81\u201396","journal-title":"J Immunol Methods"},{"key":"11768_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-01232-9","author":"H Al-Koussa","year":"2020","unstructured":"Al-Koussa H, El Mais N, Maalouf H et al (2020) Arginine deprivation: a potential therapeutic for cancer cell metastasis? A review. Cancer Cell Int. https:\/\/doi.org\/10.1186\/s12935-020-01232-9","journal-title":"Cancer Cell Int"},{"key":"11768_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0178-4","volume":"1","author":"C-T Cheng","year":"2018","unstructured":"Cheng C-T, Qi Y, Wang Y-C et al (2018) Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction. Commun Biol 1:178","journal-title":"Commun Biol"},{"key":"11768_CR41","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1158\/0008-5472.CAN-08-3157","volume":"69","author":"RH Kim","year":"2009","unstructured":"Kim RH, Coates JM, Bowles TL et al (2009) Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res 69:700\u2013708","journal-title":"Cancer Res"},{"key":"11768_CR42","unstructured":"Robbins SL, Kumar V, Abbas AK et al (2010) Robbins and Cotran pathologic basis of disease. (No Title)"},{"key":"11768_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084163","volume":"25","author":"RM Mendoza","year":"2024","unstructured":"Mendoza RM, Song JH, Jung YT et al (2024) Recombinant arginine deiminase from Levilactobacillus brevis inhibits the growth of stomach cancer cells, possibly by activating the intrinsic apoptosis pathway. Int J Mol Sci 25:4163","journal-title":"Int J Mol Sci"},{"key":"11768_CR44","unstructured":"Szlosarek PW, Phillips RM (2022) Arginine deprivation therapy in cancer: Mechanisms and clinical application. Cancer Metab 10"},{"key":"11768_CR45","first-page":"9720","volume":"66","author":"PW Szlosarek","year":"2006","unstructured":"Szlosarek PW (2006) Arginine deprivation with ADI-PEG20: a novel strategy for treating arginine-auxotrophic cancers. Cancer Res 66:9720\u20139729","journal-title":"Cancer Res"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-11768-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-026-11768-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-11768-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:07:18Z","timestamp":1775815638000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-026-11768-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["11768"],"URL":"https:\/\/doi.org\/10.1007\/s11033-026-11768-0","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"assertion":[{"value":"8 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"602"}}