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Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway.

Alhosin M, León-González AJ, Dandache I, Lelay A, Rashid SK, Kevers C, Pincemail J, Fornecker LM, Mauvieux L, Herbrecht R, Schini-Kerth VB - Sci Rep (2015)

Bottom Line: Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect.Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2.This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France.

ABSTRACT
Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.

No MeSH data available.


Related in: MedlinePlus

Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the indicated times and thereafter the expression of the p53, p73, cleaved caspase 3 and UHRF1 was studied using Western blot. The control (Ctr) represents untreated cells harvested at 6 h. The data are representative of cells from six CLL patients. Cleaved caspase 3 and UHRF1 expression levels were analyzed by densitometry and represented as percentage compared with control.
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f3: Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the indicated times and thereafter the expression of the p53, p73, cleaved caspase 3 and UHRF1 was studied using Western blot. The control (Ctr) represents untreated cells harvested at 6 h. The data are representative of cells from six CLL patients. Cleaved caspase 3 and UHRF1 expression levels were analyzed by densitometry and represented as percentage compared with control.

Mentions: Activation of caspase-dependent cascade leading to apoptosis has been involved in polyphenolic extracts-mediated cell death in cancer cells including leukaemia17181920. We therefore determined the involvement of activated caspase 3, one of the main executors of apoptosis in the pro-apoptotic effect of Antho 50 in CLL cells (Fig. 3). Exposure of cells to 75 μg/mL of Antho 50 induced a time-dependent caspase 3 activation (Fig. 3). A slight increased expression of activated caspase 3 was observed already at one h and thereafter the signal increased progressively at least until 6 h (Fig. 3).


Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway.

Alhosin M, León-González AJ, Dandache I, Lelay A, Rashid SK, Kevers C, Pincemail J, Fornecker LM, Mauvieux L, Herbrecht R, Schini-Kerth VB - Sci Rep (2015)

Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the indicated times and thereafter the expression of the p53, p73, cleaved caspase 3 and UHRF1 was studied using Western blot. The control (Ctr) represents untreated cells harvested at 6 h. The data are representative of cells from six CLL patients. Cleaved caspase 3 and UHRF1 expression levels were analyzed by densitometry and represented as percentage compared with control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355738&req=5

f3: Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the indicated times and thereafter the expression of the p53, p73, cleaved caspase 3 and UHRF1 was studied using Western blot. The control (Ctr) represents untreated cells harvested at 6 h. The data are representative of cells from six CLL patients. Cleaved caspase 3 and UHRF1 expression levels were analyzed by densitometry and represented as percentage compared with control.
Mentions: Activation of caspase-dependent cascade leading to apoptosis has been involved in polyphenolic extracts-mediated cell death in cancer cells including leukaemia17181920. We therefore determined the involvement of activated caspase 3, one of the main executors of apoptosis in the pro-apoptotic effect of Antho 50 in CLL cells (Fig. 3). Exposure of cells to 75 μg/mL of Antho 50 induced a time-dependent caspase 3 activation (Fig. 3). A slight increased expression of activated caspase 3 was observed already at one h and thereafter the signal increased progressively at least until 6 h (Fig. 3).

Bottom Line: Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect.Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2.This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France.

ABSTRACT
Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.

No MeSH data available.


Related in: MedlinePlus