Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells
Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama, Japan. International journal of hematology
(Impact Factor: 1.92).
07/2010; 92(1):136-43. DOI: 10.1007/s12185-010-0627-4
All-trans retinoic acid (ATRA) is a standard drug used for differentiation therapy in acute promyelocytic leukemia. To potentiate this therapy, we examined the effect of ellagic acid (EA), a natural polyphenolic compound with antiproliferative and antioxidant properties, on the growth and differentiation of HL-60 acute myeloid leukemia cells. EA was found to induce apoptosis, which was blocked by pan-caspase inhibitor, Z-VAD-FMK. EA activated the caspase-3 pathway and enhanced the expressions of myeloid differentiation markers (CD11b, MRP-14 protein, granulocytic morphology) induced by ATRA treatment. These results indicate that EA is a potent apoptosis inducer and also effectively potentiates ATRA-induced myeloid differentiation of HL-60 cells.
Available from: Philipp Saiko
- "), to induce cell cycle arrest and apoptosis, and to act as cancer chemopreventive agents in a multitude of preclinical and animal studies (Hagiwara et al. 2010; Heber 2008; Ngo et al. 2011; Petersen and Simmonds 2003; Singh et al. 2011; Viladomiu et al. 2013; Wu and Wang 2012). "
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ABSTRACT: Epigallocatechin gallate (EGCG), ellagic acid (EA) and rosmarinic acid (RA) are natural polyphenols exerting cancer chemopreventive effects. Ribonucleotide reductase (RR; EC 18.104.22.168) converts ribonucleoside diphosphates into deoxyribonucleoside diphosphates being essential for DNA replication, which is why the enzyme is considered an excellent target for anticancer therapy. EGCG, EA, and RA dose-dependently inhibited the growth of human HL-60 promyelocytic leukemia cells, exerted strong free radical scavenging potential, and significantly imbalanced nuclear deoxyribonucleoside triphosphate (dNTP) concentrations without distinctly affecting the protein levels of RR subunits (R1, R2, p53R2). Incorporation of (14)C-cytidine into nascent DNA of tumor cells was also significantly lowered, being equivalent to an inhibition of DNA synthesis. Consequently, treatment with EGCG and RA attenuated cells in the G0/G1 phase of the cell cycle, finally resulting in a pronounced induction of apoptosis. Sequential combination of EA and RA with the first-line antileukemic agent arabinofuranosylcytosine (AraC) synergistically potentiated the antiproliferative effect of AraC, whereas EGCG plus AraC yielded additive effects. Taken together, we show for the first time that EGCG, EA, and RA perturbed dNTP levels and inhibited cell proliferation in human HL-60 promyelocytic leukemia cells, with EGCG and RA causing a pronounced induction of apoptosis. Due to these effects and synergism with AraC, these food ingredients deserve further preclinical and in vivo testing as inhibitors of leukemic cell proliferation.
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Available from: PubMed Central
- "It attenuated diet-induced symptoms of metabolic syndrome with normalization of protein levels of Nrf2, NF-κB, and CPT1 . Other than metabolic-regulating effect, EA has been reported to induce apoptosis in pancreatic and leukemia cancer cells [24, 25]. Several in vivo and in vitro studies confirmed its antiproliferative, anti-inflammatory, and antitumorigenic properties [26–28]. "
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ABSTRACT: Ellagic acid (EA) present in many fruits and nuts serves as antiproliferation, anti-inflammatory, and antitumorigenic properties. However, the effect of EA on preadipocytes adipogenesis and its mechanism(s) have not been elucidated. The present study was designed to examine the effect of EA on adipogenesis in 3T3-L1 preadipocytes and underlying mechanism(s) of action involved. Data show that EA administration decreased the accumulation of lipid droplets. The inhibition was diminished when the addition of EA was delayed to days 2-4 of differentiation. Clonal expansion was reduced in the presence of EA. FACS analysis showed that EA blocked the cell cycle at the G1/S transition. EdU incorporation also confirmed that EA refrained cell from entering S phase. Our data also revealed that the differentiation-induced protein expression of Cyclin A and phosphorylation of the retinoblastoma protein (Rb) were impaired by EA. Differentiation-dependent expression and DNA-binding ability of C/EBP α were also inhibited by EA. Alterations in cell cycle-associated proteins may be important with respect to the antiadipogenic action of EA. In conclusion, EA is capable of inhibiting adipogenesis in 3T3-L1 adipocytes possibly through reduction of Cyclin A protein expression and Rb phosphorylation. With the blocking of G1/S phase transition, EA suppresses terminal differentiation and lipid accumulation in 3T3-L1 adipocytes.
Available from: Yeqing Angela Yang
- "This fi nding provided a mechanistic link to PL3′s previously known anti-infl ammatory and cytotoxic activities in other cancer types including breast cancer and hepatocellular carcinoma (Chang et al., 2006), and offers an insightful approach to molecularly target EZH2. Additionally, a well-known anticancer agent, all-trans retinoic acid (ATRA), whose apoptosis-inducing activity has been investigated in leukemia (Drach et al., 1993; Hagiwara et al., 2010), gastric cancer (Hoang et al., 2010) and prostate cancer (Zhang, 2002), is recently evidenced to function through repression of EZH2-and DNMT3B- mediated hypermethylation of HOXB13, a member of the homeobox superfamily and an anti-proliferative transcription factor (Liu et al., 2012). EZH2 is known to recruit DNMT3B to promoter regions of specifi c gene loci since the latter does not inherently have DNA-binding domains and depends on EZH2′s presence in order to carry out DNA methylation (Vire et al., 2006). "
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ABSTRACT: The histone methyltransferase EZH2 has been in the limelight of the field of cancer epigenetics for a decade now since it was first discovered to exhibit an elevated expression in metastatic prostate cancer. It persists to attract much scientific attention due to its important role in the process of cancer development and its potential of being an effective therapeutic target. Thus here we review the dysregulation of EZH2 in prostate cancer, its function, upstream regulators, downstream effectors, and current status of EZH2-targeting approaches. This review therefore provides a comprehensive overview of EZH2 in the context of prostate cancer.
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