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This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B <jats:italic>in vitro<\/jats:italic>. <jats:sup>31<\/jats:sup>P magnetic resonance spectroscopy (MRS) indicates that LND (100\u2009mg\/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three\u2009hours, intracellular pH\u00a0(pHi) of WM983B decreased from 6.91\u2009\u00b1\u20090.03 to 6.59\u2009\u00b1\u20090.10 (p\u2009=\u20090.03), whereas extracellular pH\u00a0(pHe) of this tumor changed from 7.03\u2009\u00b1\u20090.05 to 6.89\u2009\u00b1\u20090.06 (p\u2009=\u20090.19). A decline in bioenergetics (\u03b2-NTP\/Pi) of 55\u2009\u00b1\u20095.0% (p\u2009=\u20090.03) accompanied the decline in pHi\u00a0of WM983B. Using <jats:sup>1<\/jats:sup>H MRS with a selective multiquantum pulse sequence and Hadamard localization, we show that LND induced a significant increase in tumor lactate levels (p\u2009&lt;\u20090.01). LND pre-treatment followed by DOX (10\u2009mg\/kg, i.v.) produced a growth delay of 13.7 days in WM983B (p\u2009&lt;\u20090.01 versus control), a growth delay significantly smaller than the 25.4 days that occurred with DB-1 (p\u2009=\u20090.03 versus WM983B). Differences in relative levels of glycolysis may produce differential therapeutic responses of DB-1 and WM983B melanomas.<\/jats:p>","DOI":"10.1038\/s41598-018-33019-4","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T11:28:31Z","timestamp":1537961311000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin"],"prefix":"10.1038","volume":"8","author":[{"given":"Kavindra","family":"Nath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Roman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Cheol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepan","family":"Orlovskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Muriuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Heitjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Pickup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis B.","family":"Leeper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Putt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry D.","family":"Glickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,2]]},"reference":[{"key":"33019_CR1","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1002011","volume":"363","author":"KT Flaherty","year":"2010","unstructured":"Flaherty, K. 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