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This is likely due to their ability to evade apoptosis. Therefore, inducing apoptosis in leukemia cells using innovative drug combinations may be the most effective therapeutic approach. Methods for multidrug combinations involving three or more drugs are scarce and much more complex to analyze. To address this issue, we propose an effective concentration 50 (EC\n                    <jats:sub>50<\/jats:sub>\n                    )-based, three-step method. The first step determines the lowest EC\n                    <jats:sub>50<\/jats:sub>\n                    for each drug (e.g., artemisinin, chloroquine, primaquine, mefloquine, ivermectin, moxidectin, doxorubicin, and minocycline) by analyzing four cell endpoints (e.g., cell cycle, sub-G1, mitochondrial membrane potential (\u0394\u03a8\n                    <jats:sub>m<\/jats:sub>\n                    ), autophagy (lysosomes), and cleaved caspase 3 (CC3)) on K562 cells. Step two involves establishing the deleterious effect of the EC\n                    <jats:sub>50<\/jats:sub>\n                    -based drug combination at concentrations of single drugs at 1-, \u00bd-, and \u00bc-EC\n                    <jats:sub>50<\/jats:sub>\n                    , respectively, on K562 leukemia cells. Step three involves using the optimal combined drugs to evaluate the same cellular endpoints in other non-leukemic and leukemic cells. We found that the combination of AM (1 \u00b5M), MD (10 \u00b5M), and DR (1.5 \u00b5M), i.e., at \u00bd EC\n                    <jats:sub>50<\/jats:sub>\n                    , induced cell cycle arrest in the S (25% \u00b1 13,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094) and G2\/M (55% \u00b1 18,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094) phases, a drastic loss of \u0394\u03a8\n                    <jats:sub>m<\/jats:sub>\n                    (81% \u00b1 6,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094), high lysosome accumulation (82% \u00b1 10,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094), and CC3 (83% \u00b1 13,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20094), as evidence of apoptosis in K562 and Jurkat cells and ex vivo ALL and CML cells. The combined drugs were innocuous to peripheral blood lymphocytes (PBLs) (S phase\u2009=\u200940%; G2\/M\u2009=\u200926%; \u0394\u03a8\n                    <jats:sub>m<\/jats:sub>\n                    \u2009=\u20094%; lysosomes\u2009=\u20093%; CC3\u2009=\u20094%;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093). Our approach to combining drugs has the potential to provide a new pharmacological treatment for leukemias.\n                  <\/jats:p>","DOI":"10.1007\/s12032-026-03320-8","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:37:53Z","timestamp":1784871473000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A combination of artemisinin, moxidectin, and doxorubicin drugs can selectively and efficiently induce apoptosis in acute lymphoblastic and chronic myeloid leukemia cells in vitro and ex vivo"],"prefix":"10.1007","volume":"43","author":[{"given":"Viviana","family":"Soto-Mercado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mendivil-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Jimenez-Del-Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Velez-Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"3320_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/S41572-024-00525-X","author":"L Pagliaro","year":"2024","unstructured":"Pagliaro L, Chen SJ, Herranz D, Mecucci C, Harrison CJ, Mullighan CG, et al. 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