Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells

Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, Yusuf

doi:10.1007/s13277-015-3962-5

Cited by 22 publications

(20 citation statements)

References 40 publications

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“…The result showed that pomegranate juice caused the loss of mitochondrial membrane potential [ Figure 3] which could be linked with the induction of apoptosis in A549 cells. Previous studies also showed pomegranate juice triggered apoptosis with significant increases in loss of MMP in several cell lines such as U266 multiple myeloma cells (18), human colon cancer cells (6) and prostate cancer cell (19). The effect of pomegranate juice on cytochrome c release in A549 cells.…”

Section: Pomegranate Disrupt the Mitochondrial Membrane Potential (Mmmentioning

confidence: 84%

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells

Ghani¹,

Malek²,

Abdullah³

2018

IJET

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Lung cancer is the most common type of cancer which the mortality rate increases year by year. Therapeutic drugs could not control the progression of cancer and it contributes to the side effects in normal cells. Thus, an alternative strategy using natural product becomes a focus today. Punica granatum, known as pomegranate has demonstrated the anti-proliferative effect in A549 cells. To further confirm its efficacy, this study aimed to investigate the type of cell death and its pathway in A549 cells. Propium Iodide staining was applied to determine the cell cycle profile changes induced by this juice. The determination of type of cell death was done using Annexin-V staining and later will be analysed using flowcytometer. The pathway to apoptosis was investigated by determining the caspase- 3, 8 and 9 activities. The findings were supported by mitochondrial membrane permeability assay and cytochrome c release detection which were later analysed using flowcytometer. This study revealed that pomegranate juice induced cell cycle arrest at G0/G1 phase and apoptosis through intrinsic pathway following 24 h treatment. Pomegranate juice caused loss of mitochondrial membrane permeability after 48 h [p<0.05] exposure and a release of cytochrome c in cytosol after 24 h [p<0.05] and 48 h [p<0.01] exposure in treated A549 cells. In caspases analysis, it was showed that there was activation of caspase-3 following 72 h [p<0.01] treatment and caspase-9 after 48 [p<0.01] and 72 h [p<0.05] exposure in treated A549 cells. It can be concluded that pomegranate juice able to cause A549 cell growth inhibition by inducing cell cycle arrest and apoptosis through mitochondrial pathway.

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Section: Pomegranate Disrupt the Mitochondrial Membrane Potential (Mmmentioning

confidence: 84%

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells

Ghani¹,

Malek²,

Abdullah³

2018

IJET

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“…The result showed that pomegranate juice caused the loss of mitochondrial membrane potential (Figure 3) which could be linked with the induction of apoptosis in A549 cells. Previous studies also showed pomegranate juice triggered apoptosis with significant increases in loss of MMP in several cell lines such as U266 multiple myeloma cells (Kiraz et al, 2015), human colon cancer cells (Turrini et al, 2015) and prostate cancer cell (Ismail et al, 2015).…”

Section: Pomegranate Disrupt the Mitochondrial Membrane Potential (Mmmentioning

confidence: 89%

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis Via Mitochondrial Pathway in Human Lung Aden carcinoma A549 Cells

Ghani¹,

Malek²,

Ashari³

et al. 2018

IJET

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Lung cancer is the most common type of cancer which the mortality rate increases year by year. Therapeutic drugs could not control the progression of cancer and it contributes to the side effects in normal cells. Thus, an alternative strategy using natural product becomes a focus today. Punica granatum, known as pomegranate has demonstrated the anti-proliferative effect in A549 cells. To further confirm its efficacy, this study aimed to investigate the type of cell death and its pathway in A549 cells. Propium Iodide staining was applied to determine the cell cycle profile changes induced by this juice. The determination of type of cell death was done using Annex in-V staining and later will be analyzed using flow cytometer. The pathway to apoptosis was investigated by determining the caspase- 3, 8 and 9 activities. The findings were supported by mitochondrial membrane permeability assay and cytochrome c release detection which were later analyzed using flow cytometer. This study revealed that pomegranate juice induced cell cycle arrest at G0/G1 phase and apoptosis through intrinsic pathway following 24 h treatment. Pomegranate juice caused loss of mitochondrial membrane permeability after 48 h (p<0.05) exposure and a release of cytochrome c in cytosol after 24 h (p<0.05) and 48 h (p<0.01) exposure in treated A549 cells. In caspases analysis, it was showed that there was activation of caspase-3 following 72 h (p<0.01) treatment and caspase-9 after 48 (p<0.01) and 72 h (p<0.05) exposure in treated A549 cells. It can be concluded that pomegranate juice able to cause A549 cell growth inhibition by inducing cell cycle arrest and apoptosis through mitochondrial pathway.

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“…In particular, it has been reported that the anthocyanins, which are major components of PGJ, were found to have binding affinity against eicosanoid receptors (e.g., peroxisome proliferator-activated receptors α and γ), by this way regulating gene expression and suppressing chemically induced carcinogenesis [48]. Several data demonstrated that the pomegranate leaves, stem and flower extracts modulate cell cycle progression and induce apoptosis in human MM cells through G2/M and S phase cell cycle arrest and mitochondrial membrane permeabilization [49]. It has also been reported that pomegranate induces apoptosis in leukemia cell lines and its polyphenols are responsible for these pro-apoptotic properties [50].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

et al. 2016

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Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

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Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells

Cited by 22 publications

References 40 publications

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells

Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis Via Mitochondrial Pathway in Human Lung Aden carcinoma A549 Cells

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

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