Chloroquine Against Malaria, Cancers and Viral Diseases

Overview

Journal Drug Discov Today

Specialty Pharmacology

Date 2020 Sep 18

PMID 32947043

Citations 40

Authors

Wenmin Zhou

Hui Wang

Yuqi Yang

Zhe-Sheng Chen

Chang Zou

Jianye Zhang

Affiliations

Soon will be listed here.

Abstract

Quinoline (QN) derivatives are often used for the prophylaxis and treatment of malaria. Chloroquine (CQ), a protonated, weakly basic drug, exerts its antimalarial effect mainly by increasing pH and accumulating in the food vacuole of the parasites. Repurposing CQ is an emerging strategy for new indications. Given the inhibition of autophagy and its immunomodulatory action, CQ shows positive efficacy against cancer and viral diseases, including Coronavirus 2019 (COVID-19). Here, we review the underlying mechanisms behind the antimalarial, anticancer and antiviral effects of CQ. We also discuss the clinical evidence for the use of CQ and hydroxychloroquine (HCQ) against COVID-19.

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References

Gupta N, Agrawal S, Ish P . Chloroquine in COVID-19: the evidence. Monaldi Arch Chest Dis. 2020; 90(1). DOI: 10.4081/monaldi.2020.1290. View

Hu J, Zhang Y, Jiang X, Zhang H, Gao Z, Li Y . ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine. J Exp Clin Cancer Res. 2019; 38(1):225. PMC: 6540563. DOI: 10.1186/s13046-019-1201-4. View

Viry E, Paggetti J, Baginska J, Mgrditchian T, Berchem G, Moussay E . Autophagy: an adaptive metabolic response to stress shaping the antitumor immunity. Biochem Pharmacol. 2014; 92(1):31-42. DOI: 10.1016/j.bcp.2014.07.006. View

Verma R, Khanna P, Chawla S . Malaria vaccine can prevent millions of deaths in the world. Hum Vaccin Immunother. 2013; 9(6):1268-71. PMC: 3901816. DOI: 10.4161/hv.23950. View

Rajendran P, Li F, Shanmugam M, Vali S, Abbasi T, Kapoor S . Honokiol inhibits signal transducer and activator of transcription-3 signaling, proliferation, and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J Cell Physiol. 2011; 227(5):2184-95. DOI: 10.1002/jcp.22954. View

Gao L, Sun X, Zhang Q, Chen X, Zhao T, Lu L . Histone deacetylase inhibitor trichostatin A and autophagy inhibitor chloroquine synergistically exert anti-tumor activity in H-ras transformed breast epithelial cells. Mol Med Rep. 2018; 17(3):4345-4350. PMC: 5802205. DOI: 10.3892/mmr.2018.8446. View

Mushtaque M, Shahjahan . Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: a review. Eur J Med Chem. 2014; 90:280-95. DOI: 10.1016/j.ejmech.2014.11.022. View

Kimura T, Takabatake Y, Takahashi A, Isaka Y . Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer Res. 2013; 73(1):3-7. DOI: 10.1158/0008-5472.CAN-12-2464. View

Gevers S, Kwa M, Wijnans E, van Nieuwkoop C . Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clin Microbiol Infect. 2020; 26(9):1276-1277. PMC: 7228887. DOI: 10.1016/j.cmi.2020.05.006. View

10.

Datta S, Choudhury D, Das A, Mukherjee D, Dasgupta M, Bandopadhyay S . Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway. Apoptosis. 2019; 24(5-6):414-433. DOI: 10.1007/s10495-019-01526-y. View

11.

Li Q, Yuan D, Ma L, Ma C, Liu Y, Lv T . Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion. Tumour Biol. 2016; 37:16249–16258. DOI: 10.1007/s13277-016-5441-z. View

12.

Milner Jr D . Malaria Pathogenesis. Cold Spring Harb Perspect Med. 2017; 8(1). PMC: 5749143. DOI: 10.1101/cshperspect.a025569. View

13.

Liu S, Cai X, Xia L, Jiang C, Chen P, Wang X . Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide. Oncol Lett. 2018; 15(2):2024-2030. PMC: 5774501. DOI: 10.3892/ol.2017.7488. View

14.

Guo Y, Cao Q, Hong Z, Tan Y, Chen S, Jin H . The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020; 7(1):11. PMC: 7068984. DOI: 10.1186/s40779-020-00240-0. View

15.

Arnaout A, Robertson S, Pond G, Lee H, Jeong A, Ianni L . A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients. Breast Cancer Res Treat. 2019; 178(2):327-335. DOI: 10.1007/s10549-019-05381-y. View

16.

Popovici J, Vantaux A, Primault L, Samreth R, Piv E, Bin S . Therapeutic and Transmission-Blocking  Efficacy of Dihydroartemisinin/Piperaquine and Chloroquine against Plasmodium vivax Malaria, Cambodia. Emerg Infect Dis. 2018; 24(8):1516-1519. PMC: 6056113. DOI: 10.3201/eid2408.170768. View

17.

Bishop E, Bradshaw T . Autophagy modulation: a prudent approach in cancer treatment?. Cancer Chemother Pharmacol. 2018; 82(6):913-922. PMC: 6267659. DOI: 10.1007/s00280-018-3669-6. View

18.

Garcia-Serradilla M, Risco C, Pacheco B . Drug repurposing for new, efficient, broad spectrum antivirals. Virus Res. 2019; 264:22-31. PMC: 7114681. DOI: 10.1016/j.virusres.2019.02.011. View

19.

Varisli L, Cen O, Vlahopoulos S . Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways. Immunology. 2019; 159(3):257-278. PMC: 7011648. DOI: 10.1111/imm.13160. View

20.

Sinkeler F, Berger F, Muntinga H, Jansen M . The risk of QTc-interval prolongation in COVID-19 patients treated with chloroquine. Neth Heart J. 2020; 28(7-8):418-423. PMC: 7346846. DOI: 10.1007/s12471-020-01462-6. View