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Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.

Salimi A, Roudkenar MH, Sadeghi L, Mohseni A, Seydi E, Pirahmadi N, Pourahmad J - Redox Biol (2015)

Bottom Line: Based on our results EA decreased the percentage of viable cells and induced apoptosis.EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects.Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

No MeSH data available.


Related in: MedlinePlus

EA induced apoptosis in CLL B-lymphocytes. Freshly isolated and purified CLL B-lymphocytes were treated with either EA-free medium containing 0.05% (v/v) DMSO (unexposed control) or 25 µM EA for 6, 12 and 24 h. Early apoptosis was measured by the annexin V assay using flow cytometry at 6, 12 and 24 h after incubation in both groups. As shown in this figure, pretreatment with BHT and Cs.A significantly inhibited apoptosis in the CLL mitochondria (graph J, graph I). The summarized apoptotic data was demonstrated at graph K. Results are expressed as means±SD, n=5, *p<0.01 vs. respective control.
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f0010: EA induced apoptosis in CLL B-lymphocytes. Freshly isolated and purified CLL B-lymphocytes were treated with either EA-free medium containing 0.05% (v/v) DMSO (unexposed control) or 25 µM EA for 6, 12 and 24 h. Early apoptosis was measured by the annexin V assay using flow cytometry at 6, 12 and 24 h after incubation in both groups. As shown in this figure, pretreatment with BHT and Cs.A significantly inhibited apoptosis in the CLL mitochondria (graph J, graph I). The summarized apoptotic data was demonstrated at graph K. Results are expressed as means±SD, n=5, *p<0.01 vs. respective control.

Mentions: The apoptosis was further quantified by the externalization of PS, assessed by annexin V-PI double staining at 6,12 and 24 h following the exposure with ellagic acid. The percentage of annexin V+/PI− cells (CD19-gated) increased to 6.73 , 11.35 and 28.16 in CLL B-lymphocytes at 6,12 and 24 h after exposure with 25 µM ellagic acid, respectively, were significantly higher than those of untreated cancerous control B-lymphocytes (all p<0.01) (Fig. 2E–H). While for healthy B-lymphocytes, EA (25 µM) treatment did not induce early apoptosis (Fig. 2A–D). Based on these data, EA appeared to have selective significant apoptotic activity toward CLL B-lymphocytes. Besides, we tested the pre treating effect of BHT and Cs.A on EA induced apoptosis in CLL B-lymphocytes within 24 h, Our findings showed that both compounds significantly decreased apoptosis% in EA treated cancerous B-lymphocytes (Fig. 2I and J). These results again confirms the role of a ROS mediated mitochondrial pathway in EA induced apoptosis.


Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.

Salimi A, Roudkenar MH, Sadeghi L, Mohseni A, Seydi E, Pirahmadi N, Pourahmad J - Redox Biol (2015)

EA induced apoptosis in CLL B-lymphocytes. Freshly isolated and purified CLL B-lymphocytes were treated with either EA-free medium containing 0.05% (v/v) DMSO (unexposed control) or 25 µM EA for 6, 12 and 24 h. Early apoptosis was measured by the annexin V assay using flow cytometry at 6, 12 and 24 h after incubation in both groups. As shown in this figure, pretreatment with BHT and Cs.A significantly inhibited apoptosis in the CLL mitochondria (graph J, graph I). The summarized apoptotic data was demonstrated at graph K. Results are expressed as means±SD, n=5, *p<0.01 vs. respective control.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588415&req=5

f0010: EA induced apoptosis in CLL B-lymphocytes. Freshly isolated and purified CLL B-lymphocytes were treated with either EA-free medium containing 0.05% (v/v) DMSO (unexposed control) or 25 µM EA for 6, 12 and 24 h. Early apoptosis was measured by the annexin V assay using flow cytometry at 6, 12 and 24 h after incubation in both groups. As shown in this figure, pretreatment with BHT and Cs.A significantly inhibited apoptosis in the CLL mitochondria (graph J, graph I). The summarized apoptotic data was demonstrated at graph K. Results are expressed as means±SD, n=5, *p<0.01 vs. respective control.
Mentions: The apoptosis was further quantified by the externalization of PS, assessed by annexin V-PI double staining at 6,12 and 24 h following the exposure with ellagic acid. The percentage of annexin V+/PI− cells (CD19-gated) increased to 6.73 , 11.35 and 28.16 in CLL B-lymphocytes at 6,12 and 24 h after exposure with 25 µM ellagic acid, respectively, were significantly higher than those of untreated cancerous control B-lymphocytes (all p<0.01) (Fig. 2E–H). While for healthy B-lymphocytes, EA (25 µM) treatment did not induce early apoptosis (Fig. 2A–D). Based on these data, EA appeared to have selective significant apoptotic activity toward CLL B-lymphocytes. Besides, we tested the pre treating effect of BHT and Cs.A on EA induced apoptosis in CLL B-lymphocytes within 24 h, Our findings showed that both compounds significantly decreased apoptosis% in EA treated cancerous B-lymphocytes (Fig. 2I and J). These results again confirms the role of a ROS mediated mitochondrial pathway in EA induced apoptosis.

Bottom Line: Based on our results EA decreased the percentage of viable cells and induced apoptosis.EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects.Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

No MeSH data available.


Related in: MedlinePlus