Exploiting intracellular iron and iron-rich compounds to effect tumor cell lysis

Payne, Anthony G.

doi:10.1016/s0306-9877(03)00110-5

Cited by 5 publications

(5 citation statements)

References 10 publications

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“…As the iron storage in tumor cells is generally decreased compared to that of erythrocytes but increased in tumor cells if compared to normal cells [81], the question arises as to whether iron may also play a role in the inhibitory action of artemisinins towards tumor cells [116]. The growth rate of a tumor was significantly slowed down by daily oral administration of ferrous sulfate followed by dihydroartemisinin.…”

Section: Mechanistic Basis For Common Modes Of Action Of Artemisinin mentioning

confidence: 99%

Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside

Efferth¹

2007

Planta Med

258

168

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Medicinal herbs from TCM hold a unique position since an enormous variety of drugs from plant origin is founded on more than 5000 years of tradition [1], [2]. Hence, it is assumed that many ineffective prescriptions have disappeared thereby significantly improving the prospect for identifying novel active constituents from TCM [3], [4]. Our interest in natural products from TCM was triggered in the 1990 s by sesquiterpene lactones of the artemisinin type from Artemisia annua L. [5]. The Artemisia genus is known to contain many bioactive compounds [6]. Apart from artemisinin, which is in the focus of the present review, we have analyzed cellular and molecular mechanisms of chemically characterized natural products derived from TCM. Among them were known compounds with still insufficiently defined modes of action, which were investigated by us with molecular biological and pharmacogenomic approaches, i. e., arsenic trioxide, ascari

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Section: Mechanistic Basis For Common Modes Of Action Of Artemisinin mentioning

confidence: 99%

Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside

Efferth¹

2007

Planta Med

258

168

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“…To validate these results obtained by correlation analyses, cell lines over-expressing MDR1/P-glycoprotein as well as other drug resistance-conferring genes were used. AS was shown similarly active towards drug-sensitive and multidrug resistant cell lines (Efferth et al, 2002;2003). Likewise, methotrexate-resistant CEM/MTX1500LV cells with an amplification of the dihydrofolate reductase (DHFR) gene and hydroxyurea-resistant CEM/HUR90 cells with over-expression of ribonucleotide reductase (RRPM2) were not cross-resistant to AS.…”

Section: Multidrug Resistancementioning

confidence: 97%

“…Molecular, cellular and physiological studies have demonstrated that, depending on the tissue type and experimental system, ART and its derivatives arrest cell growth, induce an apoptotic response, alter hormone responsive properties and/or inhibit angiogenesis of human cancer cells. The Developmental Therapeutics Program of the National Cancer Institute (NCI), USA, which analyzed the activity of AS on 55 human cancer cell lines (IC 50 values shown between nano-to micro-molar range, depending on the cancer cell line), showed that AS displays inhibitory activity against leukemia, colon, melanoma, breast, ovarian, prostate, central nervous system (CNS), and renal cancer cells (Efferth et al, 2001;2003;Efferth, 2006). DHA also has remarkable anti-neoplastic activity against pancreatic, leukemic, osteosarco-ma, and lung cancer cells (Lu et al, 2009).…”

Section: Anti-cancer Activities Of Artsmentioning

confidence: 99%

“…The expression of thioredoxin reductase and catalase correlated significantly with the IC 50 values for AS against the tumor cell lines in the NCI panel. As tumor cells contain much less iron than erythrocytes, but more than other normal tissues (Shterman et al, 1991), the question arises as to whether iron may be critical for ART's activity against tumor cells (Payne, 2003). The growth of tumors in rats was significantly retarded by daily oral administration of ferrous sulfate followed by dihydroartemisinin, while treatment with each drug applied alone had no effect (Moore et al, 1995).…”

Section: Oxidative Stress Responsementioning

confidence: 99%

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The Use of Artemisinin Compounds as Angiogenesis Inhibitors to Treat Cancer

Li¹,

Weina²,

Hickman³

2013

Research Directions in Tumor Angiogenesis

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malarial drugs. Semisynthetic ARTs are obtained from dihydroartemisinin (DHA), which is the reduced lactol derivative of ART, the main active metabolite of ARTs (Li et al., 1998). The first generation of semisynthetic ARTs includes the lipophilic arts, arteether (AE) and artemether (AM), while artesunate (AS) is the water soluble derivative (Li and Weina, 2011). AS and its bioactive metabolite, DHA, have been the topic of considerable research attention in recent years for both anti-cancer and antimalarial indications. The key structural feature in all of the ART-related molecules that mediates their antimalarial activity, and some of their anti-cancer activities, is an endoperoxide bridge. The endoperoxides are a promising class of antimalarial drugs which may meet the dual challenges posed by drug-resistant parasites and the rapid progression of malarial illness. Of the available derivatives, AS has the most favorable pharmacological profile for use in ART-based combination therapy treatment of uncomplicated malaria and intravenous therapy of severe malaria (Li and Weina, 2010a). The effectiveness of AS has been mostly attributed to its rapid and extensive hydrolysis to DHA (

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“…After the release of singlet oxygen only benzoic acid is left over. Being a peroxide, artemisinin, when it comes into contact with iron, especially with heme, generates an oxygen free radical which is converted into singlet oxygen ( 1 O 2 ) [76] most probably by the Russell mechanism [77,78]. Singlet oxygen is a very aggressive chemical species, and will very rapidly reacts with any nearby biomolecules.…”

Section: Theory Of Singlet Oxygen: Epoxidation Of Double Bonds Etcmentioning

confidence: 99%

Chemical Instability Determines the Biological Action of the Artemisinins

Jansen¹,

Soomro²

2007

CMC

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Artemisinin is a sesquiterpene compound of plant origin. It has a low molecular weight, and it contains five oxygen atoms, two in a lactone function, one is part of a seven membered ring system and two forms a peroxide function bridging over the seven-membered ring. It is a highly energetic molecule prone to lose its activity if circumstances permit. Reduction of its lactone function into dihydroartemisinin makes derivatization easy. Esterification and ether formation contribute to stability. Dihydroartemisinin exists preferably in a beta epimeric format but flip-flops with the alpha epimer. Solvation effects play a role. In doing so, open forms are created and they contribute to the instability, both of the peroxide and of the seven-membered ring. Artemisinins constitute a remarkable class of compounds which display instability both biologically and chemically due to the presence of various functional groups. Activity ranges from a wonderful action against a series of parasites, in particular malaria and schistosomiasis, to bacteria, fungi and selected viruses. The latest developments indicate a potential use in adjuvant cancer chemotherapy. The built-in chemical instability, necessary for biological action, causes serious pharmaceutical problems and only a restricted number of derivatives are useful. Problems are accelerated under tropical conditions and the basic active drug dihydroartemisinin cannot be used as such since it is prone to accelerated breakdown into a series of inactive products. The pitfalls of chemical instability and pharmaceutical stability are discussed in relation to the current uses of the drugs.

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Exploiting intracellular iron and iron-rich compounds to effect tumor cell lysis

Cited by 5 publications

References 10 publications

Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside

Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside

The Use of Artemisinin Compounds as Angiogenesis Inhibitors to Treat Cancer

Chemical Instability Determines the Biological Action of the Artemisinins

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