Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Augustin, Yolanda; Staines, Henry M.; Krishna, Sanjeev

doi:10.1016/j.pharmthera.2020.107706

Cited by 69 publications

(40 citation statements)

References 85 publications

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“…They kill malaria parasites and cancer cells by releasing free radicals which damage the mitochondria and cause apoptosis [ 77 , 78 ]. Arts also target the translationally controlled tumor protein (TCTP) promoting its downregulation and cell apoptosis [ [79] , [80] , [81] ]. These reports look contradictory to our present findings describing artemether's neuroprotective effect on stroke.…”

Section: Discussionmentioning

confidence: 99%

Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway

Peng

Zhao

et al. 2021

Redox Biology

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Ischemic stroke is one of the leading causes of death and disability among adults. Despite the economic burden of the disease, available treatment options are still very limited. With the exception of anti-thrombolytics and hypothermia, current therapies fail to reduce neuronal injury, neurological deficits and mortality rates, suggesting that the development of novel and more effective therapies against ischemic stroke is urgent. In the present study, we found that artemether, which has been used in the clinic as an anti-malarial drug, was able to improve the neurological deficits, attenuate the infarction volume and the brain water content in a middle cerebral artery occlusion (MCAO) animal model. Furthermore, artemether treatment significantly suppressed cell apoptosis, stimulated cell proliferation and promoted the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), P90 rsk and cAMP responsive element-binding protein (CREB). Artemether protective effect was attenuated by PD98059, an ERK1/2 inhibitor, administration. Similarly, in oxygen-glucose deprivation/reperfusion (OGD/RP) cell models, artemether pre-treatment induced the suppression of the intracellular ROS, the down-regulation of LDH activity, the reduction of caspase 3 activity and of the apoptosis cell rate and reversed the decrease of mitochondrial membrane potential. As with MCAO animal model, artemether promoted the activation of Erk1/2-P90 rsk -CREB signaling pathway. This effect was blocked by the inhibition or knock-down of ERK1/2. The present study provides evidences of the neuroprotective effect of artemether unravelling its potential as a new therapeutic candidate for the prevention and treatment of stroke.

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Section: Discussionmentioning

confidence: 99%

Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway

Peng

Zhao

et al. 2021

Redox Biology

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“…To date, apart from erastin and RSL3 as ferroptosis-inducing agents (FIN), several conventional chemotherapeutic drugs (Gout et al, 2001) have shown enhanced therapeutic effects related to ferroptosis. The canonical antimalarial drug artemisinin and its derivatives have been demonstrated as having great value in anticancer therapy (Augustin et al, 2020). Chen G. Q. et al ( 2020) reported that artemisinin can trigger ferroptosis by increasing cellular free iron Dihydroartemisinin (DHA), a classical artemisinin derivative, has also been shown to have initiatory effect on ferroptosis in both leukemia cells and head and neck squamous carcinoma cells (HNSCC), as reported by recent studies (Lin et al, 2016;Du et al, 2019).…”

Section: Ferroptosis Potential Value In Neoplastic Diseasesmentioning

confidence: 99%

Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

Yuan

Gao

Wang

et al. 2021

Front. Cell Dev. Biol.

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Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy.

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“…Accordingly, the mechanism of artemisinin compounds sensitizing tumor cells to ferroptosis is via regulating intracellular iron homeostasis. Previous clinical trials have shown the excellent safety and tolerability of artemisinin; therefore, using artemisinin as a proferroptotic agents can be a potential strategy for anticancer therapy [92].…”

Section: 2mentioning

confidence: 99%

The Molecular Mechanisms of Regulating Oxidative Stress-Induced Ferroptosis and Therapeutic Strategy in Tumors

Zhu

Xiong

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Ferroptosis is an atypical form of regulated cell death, which is different from apoptosis, necrosis, pyroptosis, and autophagy. Ferroptosis is characterized by iron-dependent oxidative destruction of cellular membranes following the antioxidant system’s failure. The sensitivity of ferroptosis is tightly regulated by a series of biological processes, the metabolism of iron, amino acids, and polyunsaturated fatty acids, and the interaction of glutathione (GSH), NADPH, coenzyme Q10 (CoQ10), and phospholipids. Elevated oxidative stress (ROS) level is a hallmark of cancer, and ferroptosis serves as a link between nutrition metabolism and redox biology. Targeting ferroptosis may be an effective and selective way for cancer therapy. The underlying molecular mechanism of ferroptosis occurrence is still not enough. This review will briefly summarize the process of ferroptosis and introduce critical molecules in the ferroptotic cascade. Furthermore, we reviewed the occurrence and regulation of reduction-oxidation (redox) for ferroptosis in cancer metabolism. The role of the tumor suppressor and the epigenetic regulator in tumor cell ferroptosis will also be described. Finally, old drugs that can be repurposed to induce ferroptosis will be characterized, aiming for drug repurposing and novel drug combinations for cancer therapy more efficiently and economically.

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Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Cited by 69 publications

References 85 publications

Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway

Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway

Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

The Molecular Mechanisms of Regulating Oxidative Stress-Induced Ferroptosis and Therapeutic Strategy in Tumors

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