Distinct Combinatorial Effects of the Plant Polyphenols Curcumin, Carnosic Acid, and Silibinin on Proliferation and Apoptosis in Acute Myeloid Leukemia Cells

Pesakhov, Stella; Khanin, Marina; Studzinski, George P.; Danilenko, Michael

doi:10.1080/01635581003693082

Cited by 71 publications

(75 citation statements)

References 47 publications

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“…However, epicatechin potentiated the effect of curcumin at lower concentrations, whereas high concentrations of the flavonoid acted antagonistically with curcumin. Our results are consistent with those reported from other studies of cytotoxic effects from a combination of different polyphenols, which often depend on the type of interaction and concentration of compounds [26] .…”

Section: Discussionsupporting

confidence: 83%

“…Phosphorylated histone H2AX (γ-H2AX) was detected exert a cytotoxic effect in AML cells [7] and curcumin, isolated from the rhizome Curcuma longa L. and with broad-spectrum anticancer properties, is an example [8] . Curcumin not only inhibits multiple pathways on different levels that are often overexpressed in cancer cells but also sensitizes them to apoptosis; in cancer cells resistant to apoptosis, curcumin can induce an alternative cell death, such as a mitotic catastrophe [8][9][10] .…”

Section: Cell Staining and Analysis For γH2ax And The Cell Cyclementioning

confidence: 99%

“…The use of curcumin in combination with other polyphenols may potentiate its effectiveness through synergistic interactions [26] . Furthermore, cancer is a clonal disease, and individual clones of cells differ in sensitivity to chemotherapy and fall in mutual interactions [27] .…”

Section: Cell Staining and Analysis For γH2ax And The Cell Cyclementioning

confidence: 99%

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Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

Papież¹,

Krzyściak²

2017

JUMD

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How to cite this article: Papież MA, Krzyściak W. Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line. J Unexplored Med Data 2017;2:52-9. Aim:The low bioavailability of curcumin, a polyphenol, limits its use as an antitumor agent. Identifying mechanisms to improve the bioavailability and effectiveness of curcumin can modify utilization of other plant-derived phenolic compounds. This study was conducted with an aim to determine the influence of some flavonoids on the effects of curcumin in an HL-60 cell line. Methods: Cells were incubated in the presence of different concentrations of curcumin and several flavonoids for 20 h. Cytotoxicity was evaluated using propidium iodide staining. The evaluation of γH2AX expression using a specific antibody, together with study of the cell cycle, was analyzed using flow cytometry. Results: A synergistic effect was obtained only using a combination of curcumin and lower concentrations of epicatechin. The low concentration of quercetin exerted an additive effect only in combination with curcumin. Moreover, incubation with curcumin and epicatechin resulted in a significant increase in the γH2AX level. Conclusion: Combination treatment with epicatechin and curcumin can potentially be considered for improving the effectiveness and bioavailability of curcumin in cell lines of myeloid leukemia. Key words:Polyphenols, cytotoxic effect, γ-H2AX, flow cytometry, HL-60 cell line ABSTRACTArticle history:

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Section: Discussionsupporting

confidence: 83%

Section: Cell Staining and Analysis For γH2ax And The Cell Cyclementioning

confidence: 99%

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Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

Papież¹,

Krzyściak²

2017

JUMD

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“…Several studies indicate that extracts of the plant rosemary (Rosemarinus officinalis), which is rich in polyphenols, inhibit both tumour initiation and progression in mice and rat models due to its inherent high anti-oxidant activity [7,8]. Carnosic acid (CA), the major polyphenolic diterpene of rosemary, has been shown to possess anti-inflammatory as well as antiproliferative activity in HL-60 and U937 myeloblastic cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells

et al. 2012

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This study investigates the efficacy of carnosic acid (CA), a polyphenolic diterpene, isolated from the plant rosemary (Rosemarinus officinalis), on androgen-independent human prostate cancer PC-3 cells. CA induced anti-proliferative effects in PC-3 cells in a concentration- and time-dependent manner, which was due to apoptotic induction as evident from flow-cytometry, DNA laddering and TUNEL assay. Apoptosis was associated with the activation of caspase-8, -9, -3 and -7, increase in Bax:Bcl-2 ratio, release of cytochrome-c and decrease in expression of inhibitor of apoptosis (IAP) family of proteins. Apoptosis was attenuated upon pretreatment with specific inhibitors of caspase-8 (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) suggesting the involvement of both intrinsic and extrinsic apoptotic cascades. Further, apoptosis resulted from the inhibition of IKK/NF-κB pathway as evident from decreased DNA binding activity, nuclear translocation of p50 and p65 and IκBα phosphorylation. The down-regulation of IKK/NF-κB was associated with inhibition of Akt phosphorylation and its kinase activity with a concomitant increase in the serine/threonine protein phosphatase 2A (PP2A) activity. Pharmacologic inhibition of PP2A by okadaic acid and calyculin A, significantly reversed CA-mediated apoptotic events in PC-3 cells indicating that CA induced apoptosis by activation of PP2A through modulation of Akt/IKK/NF-κB pathway. In addition, CA induced apoptosis in another androgen refractory prostate cancer DU145 cells via intrinsic pathway as evidenced from the activation of caspase 3, cleavage of PARP, increase in Bax:Bcl-2 ratio and cytochrome-c release. Carnosic acid, therefore, may have the potential for use in the prevention and/or treatment of prostate cancer.

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“…Cellular mechanisms involved in the effects of carnosic acid include up-regulation of Nuclear factor (erythroid-derived 2)-like 2 (Nfr2) activity [8, 13,55,56], preservation of mitochondrial respiratory function [11,56], mitochondrial depolarization [47], cytochrome-c release [36], increase in Bax:Bcl-2 ratio [36], caspase activation [36,37], up-regulation of NAD + -dependent deacetylase SIRT1 [2], glutathione S-transferase [8,57], death receptor (DR)5 [19], Bcl-2 interacting mediator of cell death (Bim) [19] and p53 up-regulated modulator of apoptosis (PUMA) [19] expression, down-regulation of c-FLIP and Bcl-2 expression [19] as well as stimulation of PGE 2 synthesis [15]. Signaling involved in the effect of carnosic acid further includes phosphatidylinositol 3-kinase (PI3K)/Akt [26,[46][47][48][49], nuclear factor-kappa B (NF-κB) [21,49], and p38 kinase [8, 16,45,57].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Eryptosis Following Exposure to Carnosic Acid

Stockinger¹,

Bissinger²,

Bouguerra³

et al. 2015

Cell Physiol Biochem

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Background/Aims: The phenolic abietane diterpene component of rosemary and sage, carnosic acid, may either induce or inhibit apoptosis of nucleated cells. The mechanisms involved in the effects of carnosic acid include altered mitochondrial function and gene expression. Human erythrocytes lack mitochondria and nuclei but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include oxidative stress, increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), and ceramide formation. The present study explored, whether and how carnosic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to carnosic acid significantly increased the percentage of annexin-V-binding cells (2.5 µg/ml), significantly decreased forward scatter (10 µg/ml), significantly increased Fluo3 fluorescence (10 µg/ml), significantly increased ceramide abundance (10 µg/ml), significantly increased hemolysis (10 µg/ml), but significantly decreased DCFDA fluorescence (10 µg/ml). The effect of carnosic acid on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca²⁺. Conclusion: Carnosic acid triggers cell shrinkage and phospholipid scrambling of the human erythrocyte cell membrane, an effect paralleled by and/or in part due to Ca²⁺ entry and increased ceramide abundance.

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Distinct Combinatorial Effects of the Plant Polyphenols Curcumin, Carnosic Acid, and Silibinin on Proliferation and Apoptosis in Acute Myeloid Leukemia Cells

Cited by 71 publications

References 47 publications

Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

Epicatechin acts synergistically with curcumin-induced cytogenotoxic effect in acute promyelocytic leukemia HL-60 cell line

Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells

Enhanced Eryptosis Following Exposure to Carnosic Acid

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