Artemisinin-type drugs for the treatment of hematological malignancies
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REVIEW ARTICLE
Artemisinin‑type drugs for the treatment of hematological malignancies R. I. Mancuso1 · M. A. Foglio2 · S. T. Olalla Saad1 Received: 11 June 2020 / Accepted: 6 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Qinghaosu, known as artemisinin (ARS), has been for over two millennia, one of the most common herbs prescribed in traditional Chinese medicine (TCM). ARS was developed as an antimalarial drug and currently belongs to the established standard treatments of malaria as a combination therapy worldwide. In addition to the antimalarial bioactivity of ARS, anticancer activities have been shown both in vitro and in vivo. Like other natural products, ARS acts in a multi-specific manner also against hematological malignancies. The chemical structure of ARS is a sesquiterpene lactone, which contains an endoperoxide bridge essential for activity. The main mechanism of action of ARS and its derivatives (artesunate, dihydroartemisinin, artemether) toward leukemia, multiple myeloma, and lymphoma cells comprises oxidative stress response, inhibition of proliferation, induction of various types of cell death as apoptosis, autophagy, ferroptosis, inhibition of angiogenesis, and signal transducers, as NF-κB, MYC, amongst others. Therefore, new pharmaceutically active compounds, dimers, trimers, and hybrid molecules, could enhance the existing therapeutic alternatives in combating hematologic malignancies. Owing to the high potency and good tolerance without side effects of ARS-type drugs, combination therapies with standard chemotherapies could be applied in the future after further clinical trials in hematological malignancies. Keywords Artemisia annua L. · Artemisinin · Artesunate · Combination therapies · Hematological malignancies · Leukemia Abbreviations AML Acute myeloid leukemia AMoL Acute monocytic leukemia AMPK AMP-activated protein kinase AP-1 Activator protein-1 Ara-C Cytarabine ARM Artemether ARS Artemisinin ART Artesunate ATO Arsenic trioxide B-ALL B-acute lymphoblastic leukemia BM Bone marrow CML Chronic myeloid leukemia CuZnSOD Copper, zinc-superoxide dismutase * S. T. Olalla Saad [email protected] 1
Hematology and Hemotherapy Center, University of Campinas, HEMOCENTRO UNICAMP, Campinas, São Paulo, Brazil
Faculty of Pharmaceutical Science, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil
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DA Decitabine DHA Dihydroartemisinin DLBCL Diffuse large B-cell lymphoma DM Dexamethasone DX Deferoxamine ER Endoplasmic reticulum ERK Extracellular signal-regulated kinase GEM Genetically-engineered mouse GpA Glycophorin A receptor GPX1/2 Glutathione peroxidases 1 and 2 HBO2 Hyperbaric oxygen HET Dihydroethidine H2O2 Hydrogen peroxide IFN-α Interferon-α JNK C-Jun-N-terminal kinase MAPK Mitogen-activated protein kinases MM Multiple myeloma MMP Mitochondrial membrane potential MnSOD Manganese-superoxide dismutase MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide O2− Superoxide
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