{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:02:30Z","timestamp":1780470150430,"version":"3.54.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background\/aim<\/jats:title>\n                    <jats:p>Ivermectin is emerging as a potential anticancer agent. Recombinant methioninase (rMETase) targets methionine addiction of cancer and shows synergistic efficacy when combined with cancer-chemotherapy drugs. In the present study, we compared the efficacy of the rMETase combination with ivermectin versus rMETase combined with each of five first-line chemotherapeutic agents, on HCT116 human colon-cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      The half-maximal inhibitory concentrations (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) of rMETase, ivermectin, and five first-line chemotherapy drugs were determined from dose-response curves. HCT116 colon-cancer cells were then treated with each drug at its IC\n                      <jats:sub>50<\/jats:sub>\n                      concentration, either alone, or in combination with rMETase, at their IC\n                      <jats:sub>50<\/jats:sub>\n                      concentration. Cell viability was assessed after 72\u00a0h using the WST-8 assay. A chemosensitivity index (CI) was defined as the ratio of cancer-cell viability after treatment with each drug alone at its IC\n                      <jats:sub>50<\/jats:sub>\n                      to that after treatment with the same drug at its IC\n                      <jats:sub>50<\/jats:sub>\n                      concentration combined with rMETase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At the IC\n                      <jats:sub>50<\/jats:sub>\n                      concentration, ivermectin combined with rMETase (CI, 6.7\u00a0\u00b1\u00a01.9) was significantly (p &amp;lt; 0.05) more effective than rMETase combined with 5-fluorouracil (CI, 2.0\u00a0\u00b1\u00a00.7); cisplatinum (CI, 2.4\u00a0\u00b1\u00a01.5); gemcitabine (CI, 2.5\u00a0\u00b1\u00a00.7); and paclitaxel (CI, 2.8\u00a0\u00b1\u00a00.5). Only doxorubicin combined with rMETase was slightly more effective than rMETase combined with ivermectin (CI, 7.8\u00a0\u00b1\u00a01.7).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Ivermectin combined with rMETase was more effective than four of five first-line chemotherapy drugs combined with rMETase against colon-cancer cells, demonstrating additional promise of ivermectin as an anticancer drug.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1807785","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:07:05Z","timestamp":1780466825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Direct comparison of efficacy of combining ivermectin versus five first-line chemotherapy drugs with recombinant methioninase against colon-cancer cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Jinsoo","family":"Kim","sequence":"first","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]},{"name":"Department of Surgery, University of California, San Diego","place":["San Diego, CA, United States"]},{"name":"Department of Surgery, Chungnam National University College of Medicine","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghong","family":"Han","sequence":"additional","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukuan","family":"Li","sequence":"additional","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Mo","family":"Kang","sequence":"additional","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]},{"name":"Department of Surgery, University of California, San Diego","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Miyashi","sequence":"additional","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]},{"name":"Department of Surgery, University of California, San Diego","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"AntiCancer Inc.","place":["San Diego, CA, United States"]},{"name":"Department of Surgery, University of California, San Diego","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bouvet","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Diego","place":["San Diego, CA, United 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