{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:05:21Z","timestamp":1772507121004,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chemotherapy plays a key role in breast cancer therapy, but drug resistance and unwanted side effects make the treatment less effective. We propose a new combination model that combines antineoplastic drugs and antimalarials for breast cancer therapy. Cytotoxic effects of two antineoplastic agents alone and in combination with several antimalarials on MCF-7 tumor cell line was evaluated. Different concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay method. The results indicate doxorubicin (DOX) and paclitaxel (PTX) alone at concentrations of their IC50 and higher are cell growth inhibitors. Mefloquine, artesunate, and chloroquine at concentrations of their IC50 demonstrate anti-cancer activity. In combination, almost all antimalarials demonstrate higher ability than DOX and PTX alone to decrease cell viability at concentrations of IC50 and lower than their IC50. The combination of chloroquine, artesunate and mefloquine with DOX and PTX was synergic (CI &lt; 1). The combination of DOX and mefloquine after 48 h incubation demonstrated the highest cytotoxicity against MCF-7 cells, and the combination of DOX and artesunate was the most synergic. These results suggest antimalarials could act synergistically with DOX\/PTX for breast cancer therapy.<\/jats:p>","DOI":"10.3390\/biom10121623","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:06:09Z","timestamp":1606853169000},"page":"1623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["New Trends for Antimalarial Drugs: Synergism between Antineoplastics and Antimalarials on Breast Cancer Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-5042","authenticated-orcid":false,"given":"Diana","family":"Duarte","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Al. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"American Cancer Society (2019). Breast Cancer Facts & Figures 2019\u20132020, American Cancer Society."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.7314\/APJCP.2012.13.11.5903","article-title":"Synergistic effects of exemestane and aspirin on MCF-7 human breast cancer cells","volume":"13","author":"Hu","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/jnci\/djq029","article-title":"International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?","volume":"102","author":"Pagani","year":"2010","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ctrv.2008.01.007","article-title":"Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer","volume":"34","author":"Coley","year":"2008","journal-title":"Cancer Treat. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/clpt.2009.297","article-title":"Targeted Cancer Therapies in the Twenty-First Century: Lessons from Imatinib","volume":"87","author":"Stegmeier","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S1734-1140(13)71021-1","article-title":"Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells","volume":"65","author":"Wu","year":"2013","journal-title":"Pharmacol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/FPC.0b013e32833ffb56","article-title":"Doxorubicin pathways","volume":"21","author":"Thorn","year":"2011","journal-title":"Pharmacogenet. Genom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/1534735408330717","article-title":"Trastuzumab and Doxorubicin-Related Cardiotoxicity and the Cardioprotective Role of Exercise","volume":"8","author":"Wonders","year":"2009","journal-title":"Integr. Cancer Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2147\/DDDT.S56801","article-title":"Paclitaxel: New uses for an old drug","volume":"8","author":"Dong","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1517\/14656566.3.6.755","article-title":"Paclitaxel in cancer therapy","volume":"3","author":"Markman","year":"2002","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8386","DOI":"10.1158\/0008-5472.CAN-09-1504","article-title":"Inhibition of the Androgen Receptor as a Novel Mechanism of Taxol Chemotherapy in Prostate Cancer","volume":"69","author":"Gan","year":"2009","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1158\/0008-5472.CAN-06-3914","article-title":"Novel Action of Paclitaxel against Cancer Cells: Bystander Effect Mediated by Reactive Oxygen Species","volume":"67","author":"Alexandre","year":"2007","journal-title":"Cancer Res."},{"key":"ref_15","unstructured":"(2020, November 11). Taxol. Available online: https:\/\/www.breastcancer.org\/treatment\/druglist\/taxol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrd842","article-title":"Selective anticancer drugs","volume":"1","author":"Atkins","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.addr.2009.08.001","article-title":"Polymer therapeutics: Clinical applications and challenges for development","volume":"61","author":"Vicent","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Palmer, A.C., Chidley, C., and Sorger, P.K. (2019). A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity. Elife, 8.","DOI":"10.7554\/eLife.50036"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2174\/1570163811310020003","article-title":"Drugs and their Interactions","volume":"10","author":"Cokol","year":"2013","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1248\/cpb.c17-00261","article-title":"Synergistic activity of an antimetabolite drug and tyrosine kinase inhibitors against breast cancer cells","volume":"65","author":"Wu","year":"2017","journal-title":"Chem. Pharm. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Miskimins, W.K., Ahn, H.J., Kim, J.Y., Ryu, S., Jung, Y.-S., and Choi, J.Y. (2014). Synergistic Anti-Cancer Effect of Phenformin and Oxamate. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085576"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1111\/bph.13045","article-title":"Synergistic anti-tumour effects of tetrandrine and chloroquine combination therapy in human cancer: A potential antagonistic role for p21","volume":"172","author":"Mei","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12380","DOI":"10.1111\/jpi.12380","article-title":"Melatonin synergizes the chemotherapeutic effect of 5-fluorouracil in colon cancer by suppressing PI3K\/AKT and NF-\u03baB\/iNOS signaling pathways","volume":"62","author":"Gao","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1158\/1535-7163.MCT-06-0084","article-title":"Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases","volume":"5","author":"Smalley","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ygyno.2015.04.026","article-title":"Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer","volume":"138","author":"McMeekin","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1021\/cr020010d","article-title":"Biochemical Modulation of Cisplatin Mechanisms of Action: Enhancement of Antitumor Activity and Circumvention of Drug Resistance","volume":"103","author":"Fuertes","year":"2003","journal-title":"Chem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrclinonc.2016.66","article-title":"Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease","volume":"13","author":"Bianchini","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/bph.13895","article-title":"Drug repurposing screens and synergistic drug-combinations for infectious diseases","volume":"175","author":"Zheng","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.rdc.2017.04.010","article-title":"Drug Repositioning Strategies for the Identification of Novel Therapies for Rheumatic Autoimmune Inflammatory Diseases","volume":"43","author":"Grammer","year":"2017","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3332\/ecancer.2018.886","article-title":"ReDO_DB: The repurposing drugs in oncology database","volume":"12","author":"Pantziarka","year":"2018","journal-title":"Ecancermedicalscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/cncr.22562","article-title":"Prophylaxis ofPneumocystis carinii pneumonia with atovaquone in children with leukemia","volume":"109","author":"Madden","year":"2007","journal-title":"Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6587","DOI":"10.1074\/jbc.M110.210047","article-title":"Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production","volume":"286","author":"Stein","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrclinonc.2011.71","article-title":"Autophagy as a target for anticancer therapy","volume":"8","author":"Janku","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hooft van Huijsduijnen, R., Guy, R.K., Chibale, K., Haynes, R.K., Peitz, I., Kelter, G., Phillips, M.A., Vennerstrom, J.L., Yuthavong, Y., and Wells, T.N.C.C. (2013). Anticancer Properties of Distinct Antimalarial Drug Classes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082962"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Laudisi, F., Mar\u00f4nek, M., Di Grazia, A., Monteleone, G., and Stolfi, C. (2020). Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144957"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.4161\/auto.24921","article-title":"Dual inhibition of autophagy and the AKT pathway in prostate cancer","volume":"9","author":"Lamoureux","year":"2013","journal-title":"Autophagy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/gt.2012.96","article-title":"Potential for enhanced therapeutic activity of biological cancer therapies with doxycycline combination","volume":"20","author":"Tang","year":"2013","journal-title":"Gene Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.bbrc.2013.10.095","article-title":"Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition","volume":"441","author":"Kim","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17031","DOI":"10.1038\/nmicrobiol.2017.31","article-title":"Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis","volume":"2","author":"Wong","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.3892\/ol.2013.1259","article-title":"Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy in vivo","volume":"5","author":"Yan","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.canlet.2012.07.029","article-title":"Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent","volume":"326","author":"Sharma","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2147\/IDR.S151031","article-title":"Clinical utility of tafenoquine in the prevention of relapse of Plasmodium vivax malaria: A review on the mode of action and emerging trial data","volume":"12","author":"Hounkpatin","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Verbaanderd, C., Maes, H., Schaaf, M.B., Sukhatme, V.P.V.V.P., Pantziarka, P., Sukhatme, V.P.V.V.P., Agostinis, P., and Bouche, G. (2017). Repurposing Drugs in Oncology (ReDO)\u2014Chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 11.","DOI":"10.3332\/ecancer.2017.781"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.imlet.2013.07.004","article-title":"Chloroquine: Modes of action of an undervalued drug","volume":"153","author":"Lopes","year":"2013","journal-title":"Immunol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1600-0463.2012.02876.x","article-title":"Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration","volume":"120","author":"Choi","year":"2012","journal-title":"Apmis"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sasaki, K., Tsuno, N.H., Sunami, E., Tsurita, G., Kawai, K., Okaji, Y., Nishikawa, T., Shuno, Y., Hongo, K., and Hiyoshi, M. (2010). Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-370"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1016\/j.bmc.2005.12.035","article-title":"Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells","volume":"14","author":"Fan","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1097\/CAD.0b013e32832f4e50","article-title":"Hydroxychloroquine, chloroquine, and all-trans retinoic acid regulate growth, survival, and histone acetylation in breast cancer cells","volume":"20","author":"Rahim","year":"2009","journal-title":"Anticancer Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1159\/000185488","article-title":"Cell Growth Inhibition, G2\/M Cell Cycle Arrest, and Apoptosis Induced by Chloroquine in Human Breast Cancer Cell Line Bcap-37","volume":"22","author":"Jiang","year":"2008","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/07357900802427927","article-title":"Chloroquine Inhibits Colon Cancer Cell Growth In Vitro and Tumor Growth In Vivo via Induction of Apoptosis","volume":"27","author":"Zheng","year":"2009","journal-title":"Cancer Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0206467","article-title":"Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis","volume":"13","author":"Villanueva","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1086\/424663","article-title":"Primaquine Therapy for Malaria","volume":"39","author":"Baird","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1086\/379714","article-title":"Primaquine for Prevention of Malaria in Travelers","volume":"37","author":"Baird","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1038\/s41467-019-11239-0","article-title":"Antimalarial activity of primaquine operates via a two-step biochemical relay","volume":"10","author":"Camarda","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.4269\/ajtmh.2005.73.1005","article-title":"A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India","volume":"73","author":"Jha","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"871","DOI":"10.4269\/ajtmh.2005.73.871","article-title":"A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya","volume":"73","author":"Wasunna","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.1128\/AAC.00520-11","article-title":"The 8-Aminoquinoline Analogue Sitamaquine Causes Oxidative Stress in Leishmania donovani Promastigotes by Targeting Succinate Dehydrogenase","volume":"55","author":"Carvalho","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","unstructured":"(2020, November 03). Proguanil | DrugBank Online. Available online: https:\/\/go.drugbank.com\/drugs\/DB01131."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1056\/NEJM199305273282103","article-title":"Comparison of Atovaquone (566C80) with Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients with AIDS","volume":"328","author":"Hughes","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/S0140-6736(96)90671-6","article-title":"Atovaquone and proguanil for Plasmodium falciparum malaria","volume":"347","author":"Radloff","year":"1996","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27458","DOI":"10.1074\/jbc.M502319200","article-title":"Uncovering the Molecular Mode of Action of the Antimalarial Drug Atovaquone Using a Bacterial System","volume":"280","author":"Mather","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12308","DOI":"10.1038\/ncomms12308","article-title":"The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia","volume":"7","author":"Ashton","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_64","first-page":"1697","article-title":"Anti-malarial atovaquone exhibits anti-tumor effects by inducing DNA damage in hepatocellular carcinoma","volume":"8","author":"Gao","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"34084","DOI":"10.18632\/oncotarget.9122","article-title":"Repurposing atovaquone: Targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells","volume":"7","author":"Fiorillo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"33425","DOI":"10.1074\/jbc.M114.564567","article-title":"Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin","volume":"289","author":"Yang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"845","DOI":"10.2147\/OTT.S81041","article-title":"Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2","volume":"8","author":"Zhang","year":"2015","journal-title":"OncoTargets Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.yexmp.2019.01.006","article-title":"The anti-malarial drug artesunate causes cell cycle arrest and apoptosis of triple-negative MDA-MB-468 and HER2-enriched SK-BR-3 breast cancer cells","volume":"107","author":"Greenshields","year":"2019","journal-title":"Exp. Mol. Pathol."},{"key":"ref_69","unstructured":"(2016). Meyler\u2019s Side Effects of Drugs, Elsevier."},{"key":"ref_70","unstructured":"(2020, November 03). Lumefantrine | DrugBank Online. Available online: https:\/\/go.drugbank.com\/drugs\/DB06708."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the chou-talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Roell, K.R., Reif, D.M., and Motsinger-Reif, A.A. (2017). An Introduction to Terminology and Methodology of Chemical Synergy\u2014Perspectives from Across Disciplines. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00158"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1080\/1061186X.2017.1405427","article-title":"Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer","volume":"26","author":"Greish","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/btm2.10082","article-title":"Schedule dependent synergy of gemcitabine and doxorubicin: Improvement of in vitro efficacy and lack of in vitro-in vivo correlation","volume":"3","author":"Vogus","year":"2018","journal-title":"Bioeng. Transl. Med."},{"key":"ref_75","first-page":"6243","article-title":"Simvastatin potentiates doxorubicin activity against MCF-7 breast cancer cells","volume":"14","author":"Buranrat","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1158\/1078-0432.CCR-13-3227","article-title":"Chloroquine Inhibits Autophagy to Potentiate Antiestrogen Responsiveness in ER+ Breast Cancer","volume":"20","author":"Cook","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/2141-9248.153609","article-title":"Anticancer effect of antimalarial artemisinin compounds","volume":"5","author":"Das","year":"2015","journal-title":"Ann. Med. Health Sci. Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/12\/1623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:40:18Z","timestamp":1760179218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/12\/1623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":77,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["biom10121623"],"URL":"https:\/\/doi.org\/10.3390\/biom10121623","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]}}}