Artemisinin-type drugs for the treatment of hematological malignancies

Mancuso, Rubia Isler; Foglio, Mary Ann; Saad, Sara Teresinha Olalla

doi:10.1007/s00280-020-04170-5

Cited by 50 publications

(33 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there is an urgent need for novel drugs which target cancer cells specifically, without side effects. ART emerges as a good option for cancer treatment with IC values ranging from 0.092 to 1.5 μM in leukemic cell lines [ 17 , 18 ]. Here, we show that the IC 50 for ART in healthy primary immune cells is 2205 μM demonstrating that ART is extremely selective and non-cytotoxic for healthy cells.…”

Section: Discussionmentioning

confidence: 99%

“…Antitumor action of ARTs mainly involves induction of apoptotic cell death, ROS generation, and cell cycle arrest [ 17 , 18 , 19 , 20 ]. Nevertheless, our understanding of the ART/mechanisms is far from complete.…”

Section: Discussionmentioning

confidence: 99%

“…Artemisinin is a semi-synthetic compound of the sesquiterpene lactone drug family, and is obtained from a Chinese plant, Artemisia annua L., used for centuries in traditional Chinese medicine and known for its antimalarial properties [ 8 ]. Artesunate (ART) is a more stable and soluble derivative of artemisinin that has been shown to exert several pharmacological actions such as anti-inflammatory [ 9 , 10 , 11 ], anti-leishmanial [ 12 , 13 ], neuroprotective [ 14 , 15 ], immunomodulatory [ 16 ], and antitumoral activity [ 17 ]. However, the effects of ART in reprogramming monocytes from a tumor-supporting phenotype into an antitumor phenotype remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells

Mancuso

Saad

Azambuja

2021

IJMS

Self Cite

View full text Add to dashboard Cite

Monocytes are components of the tumor microenvironment related to cancer progression and immune escape. Therapeutic strategies for reprogramming monocytes from a tumor-supporting phenotype towards a tumoricidal phenotype are of great interest. Artesunate (ART) may be an interesting option for cancer treatment; however, the role of ART in regulating the inflammatory tumor microenvironment has not yet been investigated. Our aim is to evaluate the immunomodulatory potential of ART in vitro in human primary monocytes. ART treatment induced an increase in inflammatory monocytes (CD14highCD16−) with HLA-DR high expression and MCP-1/IL-1β release. On the other hand, ART treatment reduced CD206 and CD163 expression, and abolished the monocyte population known as non-classical and intermediate. Leukemia cells in contact with monocytes programmed with ART presented enhanced in vitro apoptosis suggesting that monocytes acquired the ability to kill leukemic cells. ART induced changes in the monocyte phenotype were mediated by JAK2/STAT3 downregulation. The induction of immunosuppressive environment is an important step for cancer progression. ART showed an immunomodulatory activity, leading immune cells to an antitumor phenotype and could be a candidate for immunotherapy in cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells

Mancuso

Saad

Azambuja

2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…It inhibited the release of inflammatory factors to treat the diseases caused by inflammation [74] such as cancer. Some extracts of the cold-natured drugs such as tetrandrine [75], artemisinin [76], and andrographolide [77] inhibited endothelial cell proliferation, adhesion, invasion, and tube formation by targeting vascular endothelial growth factor and blocking angiogenesis and invasion of cancer cells Moreover, the highest-ranked flavours were acrid, bitter, and sweet. Acrid promotes diffusion and outthrust with dissipation-it is favourable for treating blood-stasis, blockage, and accumulations, such as ischemic stroke and cancer.…”

Section: Chinesementioning

confidence: 99%

Investigation of the Mechanism of Traditional Chinese Medicines in Angiogenesis through Network Pharmacology and Data Mining

Yun

Dan

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Although traditional Chinese medicine is effective and safe for the treatment of angiogenesis, the in vivo intervention mechanism is diverse, complex, and largely unknown. Therefore, we aimed to explore the active ingredients of traditional Chinese medicine and their mechanisms of action against angiogenesis. Data on angiogenesis-related targets were collected from GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, DrugBank, and DisGeNET. These were matched to related molecular compounds and ingredients in the traditional Chinese medicine system pharmacology platform. The data were integrated and based on the condition of degree > 1, and relevant literature, target-compound, compound-medicine, and target-compound-medicine networks were constructed using Cytoscape. Molecular docking was used to predict the predominant binding combination of core targets and components. We obtained 79 targets for angiogenesis; 41 targets were matched to 3839 compounds, of which 110 compounds were selected owing to their high correlation with angiogenesis. Fifty-five combinations in the network were obtained by molecular docking, among which PTGS2-astragalin (−9.18 kcal/mol), KDR-astragalin (−7.94 kcal/mol), PTGS2-quercetin (−7.41 kcal/mol), and PTGS2-myricetin (−7.21 kcal/mol) were top. These results indicated that the selected potential core compounds have good binding activity with the core targets. Eighty new combinations were obtained from the network, and the top combinations based on affinity were KDR-beta-carotene (−10.13 kcal/mol), MMP9-beta-sitosterol (−8.04 kcal/mol), MMP9-astragalin (−7.82 kcal/mol), and MMP9-diosgenin (−7.51 kcal/mol). The core targets included PTGS2, KDR, VEGFA, and MMP9. The essential components identified were astragalin, kaempferol, myricetin, quercetin, and β-sitosterol. The crucial Chinese medicines identified included Polygoni Cuspidati Rhizoma et Radix, Morus alba Root Bark, and Forsythiae Fructus. By systematically analysing the ingredients of traditional Chinese medicine and their targets, it is possible to determine their potential mechanisms of action against pathological angiogenesis. Our study provides a basis for further research and the development of new therapeutics for angiogenesis.

show abstract

“…Artemisinin is thought to have be one of these hepatoprotective treatments has been widely used in ancient times to reduce fever and eliminate jaundice and hepatitis [ 46 ]. Because artemisinin has consistently been considered safe and effective in clinical practice and was officially recommended by WHO in the 1980s, it is likely among the less toxic TCHM treatments with hepatoprotective effects [ 47 ]. This applies to artemisinin derivatives as well, with one study showing that an oral dose of 2.2–3.9 mg/kg/d ART (add-on oncological therapy) is safe and well tolerated by subjects with metastatic breast cancer, without altering kidney function, liver function, or routine blood tests [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

Xiong

Huang

2021

Chin Med

View full text Add to dashboard Cite

Artemisinin and its derivatives belong to a family of drugs approved for the treatment of malaria with known clinical safety and efficacy. In addition to its anti-malarial effect, artemisinin displays anti-viral, anti-inflammatory, and anti-cancer effects in vivo and in vitro. Recently, much attention has been paid to the therapeutic role of artemisinin in liver diseases. Several studies suggest that artemisinin and its derivatives can protect the liver through different mechanisms, such as those pertaining to inflammation, proliferation, invasion, metastasis, and induction of apoptosis and autophagy. In this review, we provide a comprehensive discussion of the underlying molecular mechanisms and signaling pathways of artemisinin and its derivatives in treating liver diseases. Further pharmacological research will aid in determining whether artemisinin and its derivatives may serve as promising medicines for the treatment of liver diseases in the future.

show abstract

Artemisinin-type drugs for the treatment of hematological malignancies

Cited by 50 publications

References 88 publications

Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells

Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells

Investigation of the Mechanism of Traditional Chinese Medicines in Angiogenesis through Network Pharmacology and Data Mining

Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

Contact Info

Product

Resources

About