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10 záznamů v BMČ Filtry

Článek online

TRAIL-induced apoptosis of HL60 leukemia cells: two distinct phenotypes of acquired TRAIL resistance that are accompanied with resistance to TNFalpha but not to idarubicin and cytarabine

Blood cells, molecules, & diseases. 2009 ; 42 (1) : 77-84.

Blood Cells Mol Dis
Medvik
Zdroj

TNF-related apoptosis-inducing ligand (TRAIL) is a proapoptotic cytokine implicated in cancer cell surveillance. A potential of TRAIL as a cancer-specific therapeutic agent has been proposed, either as a single agent or in combination with chemotherapy. Prolonged exposure of TRAIL-sensitive leukemia cell line, wild-type (WT) HL60 cells to recombinant soluble TRAIL or to cytostatic agents, cytarabine and idarubicin, resulted in the establishment of resistant subclones with distinct phenotypic features. The TRAIL resistant HL60 subclones were characterized by decreased expression of TRAIL and TNFalpha death receptors. These resistant subclones had impaired activation of caspases 8 and 10 in response to TRAIL and TNFalpha, decreased TRAIL-induced nuclear translocation of NFkappaB RelA/p65, and dysregulation of the expression of several apoptosis regulators. Among the TRAIL resistant HL60 subclones we identified two separate phenotypes that differed in the expression of CD14, osteoprotegerin, and several apoptosis regulators. Both these TRAIL resistant HL60 subclones were resistant to TNFalpha, suggesting disruption of the extrinsic apoptotic pathway, but not to cytostatic agents, cytarabine and idarubicin. The concurrently derived HL60 subclones were cytarabine and idarubicin-resistant but remained sensitive to TRAIL-induced apoptosis. We identified distinct pathways for the development of HL60 leukemia cell resistance to apoptosis induction. These findings are relevant for the design of more effective strategies for leukemia therapy.

Článek

Lonicera caerulea and Vaccinium myrtillus fruit polyphenols protect HaCaT keratinocytes against UVB-induced phototoxic stress and DNA damage

Journal of dermatological science. 2009 ; 56 (3) : 196-204.

Medvik
Zdroj

BACKGROUND: Sunlight is a very potent environmental factor in skin pathogenesis and can induce skin cancer. UVB irradiation is known to cause oxidative stress, inflammation and especially DNA damage. Topical application of agents with UV absorbing, antioxidant and anti-inflammatory activities is a successful strategy in the protection of the skin against UV-caused damage. OBJECTIVE: To examine the ability of the phenolic fraction of Lonicera caerulea and Vaccinum myrtillus fruits to moderate UVB-induced damage. METHODS: HaCaT keratinocytes, a well-established in vitro system for investigations on UV radiation induced cell damage, were used to assess the effects of pre- and post-treatment with L. caerulea (LCE) and V. myrtillus (VME) phenolic fractions (5-50 mg/l) on keratinocyte damage induced by a solar simulator (295-315 nm). RESULTS: In this study, a model of UVB-induced damage to HaCaT was established. LCE and VME efficiently reduced the extent of DNA breakage (especially at concentrations of 25 and 10 mg/l) together with caspase-3 and -9 activity and DNA laddering induced by UVB (100 or 200 mJ/cm(2)). LCE and VME significantly decreased RONS generation and partially diminished IL-6 expression. LCE pre-treatment also prevented keratinocytes proliferation. CONCLUSION: The results suggest that the phenolic fraction of L. caerulea and V. myrtillus fruits suppress UVB-caused injury to keratinocytes. These results now need to be demonstrated in vivo.

Článek online

Látky ovlivňující aktivitu kaspas
[Substances modifying the activity of caspases]

Česká a slovenská farmacie. 2008 ; 57 (1) : 29-34.

ISSN 1210-7816
Medvik
Zdroj

Kaspasy jsou enzymy sehrávající klíčovou roli v programované buněčné smrti – apoptóze. Dysregulace tohoto procesu vede k řadě onemocnění, na jejichž patogenezi se podílí apoptóza. Nemoci lze rozdělit do dvou skupin: na onemocnění s patologickou inhibicí apoptózy (nádorová onemocnění, některé autoimunitní nemoci) a onemocnění s patologickou indukcí apoptózy (neurodegenerativní onemocnění, AIDS). Práce uvádí přehled nejdůležitějších zástupců aktivátorů a inhibitorů kaspas, které apoptózu řídí, a jsou proto v současnosti intenzivně studovány. Spektrofotometricky byl stanoven vliv skupiny derivátů stobadinu, theofylinu a adeninu na aktivitu kaspasy 1. Studované sloučeniny vykázaly inhibiční aktivitu vůči testovanému enzymu, která u jednoho z derivátů překročila 80 %.

Caspases are enzymes which play a key role in programmed cell death – apoptosis. Dysregulation of this process results in a series of disorders in which apoptosis is involved in pathogenesis. Diseases could be divided into two groups – diseases with pathological inhibition of apoptosis (cancer, some autoimmune disorders) and diseases with pathological induction of apoptosis (neurodegenerative disorders, AIDS). The paper lists the most significant activators and inhibitors of caspases as they control apoptosis and hence they are widely studied nowadays. The effects of stobadine, theophylline and adenine derivatives on the activity of caspase 1 was investigated with the use of spectrophotometry. The compounds under study showed an inhibitory effect on the enzyme tested; in one case the inhibitory effect exceeded 80%.

Článek

Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells

Toxicology in vitro. 2008 ; 22 (4) : 1008-1017.

Toxicol In Vitro
ISSN 0887-2333
Medvik
Zdroj

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle. We conclude that both chelerythrine and dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.

Článek online

Transforming growth factor-beta1 inhibits all-trans retinoic acid-induced apoptosis

Leukemia research. 2006 ; 30 (5) : 607-623.

ISSN 0145-2126
Medvik
Zdroj

The interaction between retinoids and transforming growth factor-beta1 (TGF-beta1) leading to regulation of proliferation, differentiation and apoptosis is not still fully understood. In this study, we demonstrated that a combination treatment with all-trans retinoic acid (ATRA) and TGF-beta1 led to the enhancement of ATRA-induced suppression of cell proliferation, which is accompanied by inhibition of ATRA-induced apoptosis in human leukemia HL-60 cells. This effect was preceded by the arrest of cells in G0/G1 cell cycle phase linked with pRb protein dephosphorylation, continuous accumulation of p21 and transiently increased level of p27, inhibitors of cyclin-dependent kinases. Inhibition of ATRA-induced apoptosis by TGF-beta1 was associated with an increased level of Mcl-1 protein, an anti-apoptotic member of Bcl-2 family, but not with inhibition of mitochondrial membrane depolarization. Levels of other Bcl-2 family proteins (Bcl-2, Bcl-X(L), Bad, Bak, Bax) were unaffected by simultaneous ATRA and TGF-beta1 treatment, when compared to ATRA alone. Upregulation of c-FLIP(L) protein, an inhibitor of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), correspond with inhibition of ATRA-induced (autocrine TRAIL-mediated) caspase-8 activation and apoptosis. These results suggest that apoptosis inhibition associated with proliferation block could depend on modulation of the TRAIL apoptotic pathway and regulation of the Mcl-1 protein level. In summary, we demonstrate that the balance of processes leading to regulation of proliferation and differentiation of myeloid cells can modulate cell sensitivity to apoptosis-inducing stimuli.

Článek online

Interaction of polyunsaturated fatty acids and sodium butyrate during apoptosis in HT-29 human colon adenocarcinoma cells

European journal of nutrition. 2005 ; 44 (1) : 40-51.

Eur J Nutr
ISSN 1436-6207
Medvik
Zdroj

BACKGROUND: Dysregulation of the balance between cell growth and death in the colonic epithelium is associated with cancer promotion. Understanding how cell death in this self-renewing tissue is regulated and how it is influenced by interaction of specific dietary components, especially fat and fibre, could lead to improved treatment and prevention strategies for cancer. AIM OF THE STUDY: The effects of two types of polyunsaturated fatty acids (PUFAs)--arachidonic (AA, 20:4, n-6) or docosahexaenoic (DHA, 22:6, n-3)--on the response of human colon adenocarcinoma HT-29 cells to sodium butyrate (NaBt) were investigated. METHODS: The parameters reflecting cell proliferation and cell death were studied together with oxidative response, mitochondrial membrane potential (MMP) and changes of selected regulatory molecules associated with cell cycle (p27(Kip1) and p21(Cip1/WAF1)) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose) polymerase--PARP, Bcl-2, Bax, Bak,Mcl-1). RESULTS: We demonstrated that pre-treatment with either AA or DHA attenuated cell cycle arrest caused by NaBt which is associated with modulation of p27(Kip1), but not p21(Cip1/WAF1) protein expression. On the other hand, PUFAs sensitised HT-29 cells to NaBt-induced apoptosis. An increased amount of floating cells and cells in the subG(0)/G(1) population was associated with increased reactive oxygen species production, lipid peroxidation, decrease of MMP, activation of caspase-3 and -9, PARP cleavage, and decrease in the expression of antiapoptotic Mcl-1 protein. The observed effects were modulated by the addition of a protein synthesis inhibitor, cycloheximide, and partially reversed by the antioxidant Trolox. CONCLUSIONS: PUFAs may have beneficial effects in the colon enhancing apoptosis induced by NaBt. Alteration of cell membrane lipid composition and potentiation of oxidative processes accompanied by changes in mitochondria followed by stimulation of apoptotic cascade components play a role in these effects.

Abstrakt

Nitric oxide driven apoptosis in retinal degenerations from cell lines to animal models : COST844 Meeting the Role of Nitric Oxide in Cardiovascular System, April 8-10, 2005, Bratislava, Slovakia [abstrakt]

Cotter, T. G
Autor Cotter, T. G

Physiological research. 2005 ; Roč. 54 (č. 5) : s. 52P. (COST844 Meeting: The Role of Nitric Oxide in Cardiovascular System, April 8-10, 2005, Bratislava, Slovakia)

ISSN 0862-8408
Medvik
Zdroj