Quercetin-induced apoptosis involves increased hTERT enzyme activity of leukemic cells

Avci, Çığır Biray; Yılmaz, Suzan Güven; Dogan, Zeynep; Saydam, Güray; Dodurga, Yavuz; Ekiz, H. Atakan; Kartal, Melis; Şahin, Fahri; Baran, Yusuf; Gündüz, Cumhur

doi:10.1179/102453311x13085644680104

Cited by 32 publications

(23 citation statements)

References 33 publications

(29 reference statements)

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“…Quercetin, a naturally occurring flavonol, is one of the most abundant flavonoids universally present in fruits and vegetables (4) and has been shown to posses multiple properties capable of reducing cell growth in cancer cells (5)(6)(7). The growth-suppressive effects of quercetin in leukemic cells have been previously described; the molecular mechanisms underlying quercetin-mediated cellular responses in AML cells, however, remain poorly defined.…”

Section: Introductionmentioning

confidence: 99%

Multitarget Effects of Quercetin in Leukemia

Maso

Calgarotto

Franchi

et al. 2014

Cancer Prevention Research

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This study proposes to investigate quercetin antitumor efficacy in vitro and in vivo, using the P39 cell line as a model. The experimental design comprised leukemic cells or xenografts of P39 cells, treated in vitro or in vivo, respectively, with quercetin; apoptosis, cell-cycle and autophagy activation were then evaluated. Quercetin caused pronounced apoptosis in P39 leukemia cells, followed by Bcl-2, Bcl-xL, Mcl-1 downregulation, Bax upregulation, and mitochondrial translocation, triggering cytochrome c release and caspases activation. Quercetin also induced the expression of FasL protein. Furthermore, our results demonstrated an antioxidant activity of quercetin. Quercetin treatment resulted in an increased cell arrest in G 1 phase of the cell cycle, with pronounced decrease in CDK2, CDK6, cyclin D, cyclin E, and cyclin A proteins, decreased Rb phosphorylation and increased p21 and p27 expression. Quercetin induced autophagosome formation in the P39 cell line. Autophagy inhibition induced by quercetin with chloroquine triggered apoptosis but did not alter quercetin modulation in the G 1 phase. P39 cell treatment with a combination of quercetin and selective inhibitors of ERK1/2 and/or JNK (PD184352 or SP600125, respectively), significantly decreased cells in G 1 phase, this treatment, however, did not change the apoptotic cell number. Furthermore, in vivo administration of quercetin significantly reduced tumor volume in P39 xenografts and confirmed in vitro results regarding apoptosis, autophagy, and cell-cycle arrest. The antitumor activity of quercetin both in vitro and in vivo revealed in this study, point to quercetin as an attractive antitumor agent for hematologic malignancies. Cancer Prev Res; 7(12); 1240-50. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

Multitarget Effects of Quercetin in Leukemia

Maso

Calgarotto

Franchi

et al. 2014

Cancer Prevention Research

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“…Here, we collect natural telomerase inhibitors reported in the literature and summarize their telomerase inhibition effects, structures, possible mechanisms, and provide references for pharmaceutical chemists searching for suitable lead compounds. Table and Figures and show natural products and chemical structures that target the telomere elongation process …”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Therapeutic strategies for targeting telomerase in cancer

Chen

Tang

Shi

et al. 2019

Medicinal Research Reviews

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Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

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“…Several studies have reported the association between diet and telomere length and human telomerase activity (Gunduz et al, 2005;Avci et al, 2007Avci et al, , 2011Sahin et al, 2010;Cogulu et al, 2009). Higher plasma vitamin D was associated with increased telomere length in women .…”

Section: Dietary Biomarkers and Nutritional Intakementioning

confidence: 99%

Telomeres and Lifestyle Choices

Avcı¹

2012

Reviews on Selected Topics of Telomere Biology

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Quercetin-induced apoptosis involves increased hTERT enzyme activity of leukemic cells

Cited by 32 publications

References 33 publications

Multitarget Effects of Quercetin in Leukemia

Multitarget Effects of Quercetin in Leukemia

Therapeutic strategies for targeting telomerase in cancer

Telomeres and Lifestyle Choices

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