Beauvericin induces cytotoxic effects in human acute lymphoblastic leukemia cells through cytochrome c release, caspase 3 activation: the causative role of calcium

Jow, Guey–Mei; Chou, Cheng‐Jen; Chen, Bing–Fang; Tsai, J

doi:10.1016/j.canlet.2004.06.005

Cited by 129 publications

(109 citation statements)

References 28 publications

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“…Furthermore, the complete lack of cellular lactate dehydrogenase release indicative for necrotic cell death emphasizes the apoptotic activity of the anthelmintic drug. These results are comparable to the cytototoxic effects of the structurally related cyclohexadepsipeptides enniatins [31] and beauvericin [32,33]. Moreover, since the ionophoric activity of these cyclic peptides was suggested to contribute to their potent cytotoxicity [33,46,53], comparable modes of actions might be hypothesized for PF1022A.…”

Section: Discussionsupporting

confidence: 67%

“…PF1022A is structurally related to cyclohexadepsipeptides of the enniatin-type for which synergistic effects on antifungal drug activity were described [29,30]. Moreover, potent cytostatic and cytotoxic effects against diverse cancer cell types [31,32,33], antiangiogenic activity [34] as well as anthelmintic properties [35] could be demonstrated for these structurally related cyclohexadepsipeptides.…”

Section: Introductionmentioning

confidence: 99%

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Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Dornetshuber¹,

Kamyar²,

Rawnduzi³

et al. 2009

Biochemical Pharmacology

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Nematode infections cause human morbidity and enormous economic loss in livestock. Since resistance against currently available anthelmintics is a worldwide problem, there is a continuous need for new compounds. The cyclooctadepsipeptide PF1022A is a novel anthelmintic that binds to the latrophilin-like transmembrane receptor important for pharyngeal pumping in nematodes. Furthermore, PF1022A binds to GABA receptors, which might contribute to the anthelmintic effect. Like other cyclodepsipeptides, PF1022A acts as an ionophore. However, no correlation between ionophoric activity and anthelmintic properties was found. This is the first study describing the effect of PF1022A on mammalian cells and tissues. While channel-forming activity was observed already at very low concentrations, changes in intracellular ion concentrations and reduction of contractility in isolated guinea-pig ileum occurred at multiples of anthelmintically active concentrations.PF1022A did not induce necrotic cell death indicated by complete lack of cellular lactate dehydrogenase release. In contrast, apoptosis induction via the mitochondrial pathway was suggested for long-term drug treatment at high concentrations due to numerous apoptotic morphological changes as well as mitochondrial membrane depolarisation. Short time effects were based on cell cycle blockade in G 0 /G 1 phase. Additionally, the cell cycle and apoptosis regulating proteins p53, p21 and bax, but not Bcl-2 were shown to impact on PF1022A-induced cytotoxicity. However, since PF1022A-induced cytotoxicity was found at drug concentrations higher than those used in anthelmintic treatment, it can be suggested that PF1022A intake might not impair human or animal health. Thus, PF1022A seems to be a safe alternative to other anthelmintic drugs.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Dornetshuber¹,

Kamyar²,

Rawnduzi³

et al. 2009

Biochemical Pharmacology

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“…According to Jow et al [16] beauvericin increases antiproliferative activity against various human cancer cell lines by activating calcium sensitive cell apoptotic pathways. On the other hand, it also inhibits the directional cell motility of cancer cells at subcytotoxic concentrations as haptotaxis (outgrowth of cells) is essential for the formation of new blood vessels in tumors (angiogenesis), invasion of other tissues by cancer cells, and metastasis to the distant organs [18,36].…”

Section: Biological Activitiesmentioning

confidence: 99%

“…Additionally he also reported its effect on human breast cancer cells BC-1 and human epidermoid at 20 µg/ml. Nuclear fragmentation in the cell by the release of cytochrome C from mitochondria with the activation of caspase 3 and cellular changes in morphology with IC 50 1-2 µg/ml leads to cytotoxic effect on the cell lines of leukemia (CCRF-CEM) [16]. Calo studied the effect of mycotoxin BEA in human cell lines of myeloid origin which includes human monocytic lymphoma cells U-937 with IC 50 10 µg/ml and human promyelocytic leukemia HL-60 with IC 50 12 µg/ml [41].…”

Section: Induction Of Apoptosis and Cytotoxic And Antitumor Activitymentioning

confidence: 99%

“…Recent studies have shown that other than the above biochemical and molecular processes, other molecular mechanism of beauvericin is cell apoptosis [16,17] and other molecular targets of beauvericin are antiangiogenic activity, inhibition of metastasis prostate and breast cancer [18]. Therefore, these fungal natural products represent promising leading anticancer potential.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological and Therapeutic Potential of Beauvericin: A Short Review

Sood¹,

S²,

Hu$^{³

et al. 2017

J Proteomics Bioinform

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An entomopathogenic fungus, Beauveria spp. has been known to have numerous pharmacological and therapeutic implications, especially, in terms of human health making it a suitable for ethnopharmacological use. Beauvericin is a cyclic hexadepsipeptide mycotoxin, a novel bio-metabolite derived from this fungus, exhibiting a very potent anticancer, cytotoxic activities, antiplatelet aggregation and antimicrobial activities. The current review discusses the therapeutic potential of beauvericin including pharmacological and biological activities which will certainly draw the attention of scientific community to improve the production of beauvericin for its use in medical fields.

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Beauvericin Decreases Cell Viability of Wheat

Śrobárová

Silva

Kogan

et al. 2009

Chemistry & Biodiversity

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Recently, beauvericin (BEA) has been recognized as an important toxic compound synthesized by several Fusarium strains, infecting maize, wheat, and rice, worldwide. The effects of BEA on mammalian cells have been studied; however, its effects on the function of host plant cells are largely unknown. The purpose of our work was to assess whether BEA can affect the root and leaf cells of wheat cultivar (cv.) 'Arina' seedlings, using a cytotoxicity assay and fluorescence microscopy. Toxigenicity during wheat germination was higher in BEA-treated wheat seedlings than in non-treated seedlings (control). Leaf primordial, situated at the base and the tips of treated leaves, were more affected by BEA compared to the control when assayed in medium for cell viability measured by luminescent equipment. BEA-Treated plant cells secrete adenosine triphosphate (ATP) to the extracellular matrix and invoke more luminescence by luciferase than the non-treated seedlings. Our results were confirmed by fluorescence microscopy following '4',6-diamidino-2-phenylindole' (DAPI) staining and by confocal microscopy. In addition, the bioluminescent protein luciferase was observed in the intracellular space indicating presence of ATP. The incidence of nuclear fragmentation increased significantly in cells of seedlings treated with BEA at 40 microM concentration implying that the intracellular phytotoxin BEA plays an important role, possibly as a mediator in cell-death signalling.

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Beauvericin induces cytotoxic effects in human acute lymphoblastic leukemia cells through cytochrome c release, caspase 3 activation: the causative role of calcium

Cited by 129 publications

References 28 publications

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Effects of the anthelmintic drug PF1022A on mammalian tissue and cells

Pharmacological and Therapeutic Potential of Beauvericin: A Short Review

Beauvericin Decreases Cell Viability of Wheat

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