Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence

Wei, Shupei; Liu, Huan; Chen, Zhiyu; Wu, Yin; Liu, Yingzi; Ouyang, Qianying; Zeng, Fanchang; Nie, Yingjie; Chen, Tao

doi:10.1111/jcmm.14717

Cited by 32 publications

(21 citation statements)

References 35 publications

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“…Tocotrienol, a minor form of vitamin E, can degrade mature SREBP-2 without affecting LXR activity to maintain cholesterol homoeostasis in PCa ( 143 ). In glioma, artesunate, initially developed as an anti-malaria drug, effectively inhibits cancer cell growth and distant metastasis, and further induces cell senescence by regulating the nuclear localization of SREBP-2 and the expression of HMGCR ( 144 ). As an anthraquinone derived from many plants, emodin inhibits SREBP-2 transcriptional activity to suppress cholesterol metabolism and Akt signaling, which sensitizes HCC cells to the anti-cancer effect of sorafenib in vitro and in xenograft models ( 145 ).…”

Section: Targeting the Srebp-2-regulated Mevalonate Pathway For Cancementioning

confidence: 99%

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

Xue

Zhang

et al. 2020

Front. Oncol.

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Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and its activation and regulation by multiple signaling pathways. We then found that SREBP-2 and its regulated enzymes, including HMGCR, FPPS, SQS, and DHCR4 from the mevalonate pathway, participate in the progression of various cancers, including prostate, breast, lung, and hepatocellular cancer, as potential targets. Importantly, preclinical and clinical research demonstrated that fatostatin, statins, and N-BPs targeting SREBP-2, HMGCR, and FPPS, respectively, alone or in combination with other drugs, have been used for the treatment of different cancers. This review summarizes new insights into the critical role of the SREBP-2-regulated mevalonate pathway for cancer and its potential for targeted cancer therapy.

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Section: Targeting the Srebp-2-regulated Mevalonate Pathway For Cancementioning

confidence: 99%

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

Xue

Zhang

et al. 2020

Front. Oncol.

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“…Besides antimalarial activity, artesunate, other artemisinins, and ART-hybrid also possess profound cytotoxic activity against tumor cells [42][43][44][45][46][47]. Recently, Li et al reviewed a paper about artemisinins against hematological malignancies [48].…”

Section: Anticancer Propertiesmentioning

confidence: 99%

Antimalarial and anticancer properties of artesunate and other artemisinins: current development

Khanal

2021

Monatsh Chem

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Graphic abstract This review provides a recent perspective of artesunate and other artemisinins as antimalarial drugs and their uses in cancer therapy. Artesunate is an artemisinin derivative. Artemisinin is extracted from the plant Artemisia annua. Artemisinin and its derivatives have been the most useful drug for malarial treatment in human history. The artesunate has an advantage of a hydrophilic group over other artemisinins which makes it a more potent drug. On the industrial scale, artemisinins are synthesized in semisynthetic ways. The 1,2,4-endoperoxide bridge of artemisinins is responsible for the drug's antimalarial activity. There is the emergence of artemisinin resistance on Plasmodium falciparum and pieces of evidence suggest that it is mainly due to the mutation at Kelch13 protein of P. falciparum . Clinical trial data show that the artesunate is more favorable than quinine and other artemisinins to treat patients with severe malaria. Pieces of evidence indicate that artemisinins can be developed as anticancer drugs. The mechanism of actions on how artemisinins act as an anticancer drug involves oxidative stress, DNA damage and repair, and various types of cell deaths.

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“…Because of the superior qualities of ART, many of its effects have been investigated. ART can significantly induce cancer cell apoptosis, inhibit glioma cell growth and migration, and influence glioma cell metabolism (Wei et al, 2020). Gugliandolo et al 2018proved that ART can ameliorate traumatic brain injury (TBI)induced lesions through its anti-inflammatory activity, and its protective effects are mediated through modulation of neurotrophic factors that play crucial roles in neuronal survival.…”

Section: Terpenoids Artesunatementioning

confidence: 99%

Traditional Chinese Medicine Monomers: Novel Strategy for Endogenous Neural Stem Cells Activation After Stroke

Chen

et al. 2021

Front. Cell. Neurosci.

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Stem cell therapy, which has become a potential regenerative medical treatment and a promising approach for treating brain injuries induced by different types of cerebrovascular disease, has various application methods. Activation of endogenous neural stem cells (NSCs) can enable infarcted neuron replacement and promote neural networks’ regeneration without the technical and ethical issues associated with the transplantation of exogenous stem cells. Thus, NSC activation can be a feasible strategy to treat central nervous system (CNS) injury. The potential molecular mechanisms of drug therapy for the activation of endogenous NSCs have gradually been revealed by researchers. Traditional Chinese medicine monomers (TCMs) are active components extracted from Chinese herbs, and some of them have demonstrated the potential to activate proliferation and neurogenesis of NSCs in CNS diseases. Ginsenoside Rg1, astragaloside IV (AST), icariin (ICA), salvianolic acid B (Sal B), resveratrol (RES), curcumin, artesunate (ART), and ginkgolide B (GB) have positive effects on NSCs via different signaling pathways and molecules, such as the Wingless/integrated/β-catenin (Wnt/β-catenin) signaling pathway, the sonic hedgehog (Shh) signaling pathway, brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). This article may provide further motivation for researchers to take advantage of TCMs in studies on CNS injury and stem cell therapy.

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Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence

Cited by 32 publications

References 35 publications

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

Antimalarial and anticancer properties of artesunate and other artemisinins: current development

Traditional Chinese Medicine Monomers: Novel Strategy for Endogenous Neural Stem Cells Activation After Stroke

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