Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

Ranganathan, Santhalakshmi; Devaraj, Halagowder; Sivasithambaram, Niranjali Devaraj

doi:10.1371/journal.pone.0141370

Cited by 163 publications

(89 citation statements)

References 38 publications

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“…Results presented in this article collect a great variety of antitumor actions of either quercetin or the mentioned strategies of combination, encapsulation and derived compounds. Cell growth inhibition, in addition to apoptosis stimulation, were the main processes described as quercetin mechanisms of action against HCC, properties that have also been observed in different tumors, such as non-small cell lung cancer [64] and breast cancer [65,66]. Although almost studies associated antiproliferative activity of quercetin with alteration of several pathways, Akt/mTOR and MEK1/ERK1/2 signaling routes were mostly found to be regulated by this flavonoid, either as free drug as well as encapsulated [23,24,27,38,42].…”

Section: Discussionmentioning

confidence: 95%

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

et al. 2019

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Quercetin is a flavonoid present in fruits, vegetables and plants with antioxidant, anti-inflammatory and anticancer properties. Its beneficial activities have been demonstrated in different human pathologies, including hepatoprotective effects against liver disorders. High mortality and late diagnosis of the primary liver tumor hepatocarcinoma (HCC) makes this cancer an interesting target for the study of quercetin effects. Our aim was to systematically review antitumor activities of quercetin in HCC preclinical studies employing single, encapsulated, combined or derived quercetin forms. Literature search was conducted in PubMed, Scopus and Web of Science (WOS), and 39 studies were finally included. We found that 17 articles evaluated quercetin effects alone, six used encapsulated strategy, 10 combined this flavonoid, two decided to co-encapsulate it and only four studied effects of quercetin derivatives, highlighting that only nine included in vivo models. Results evidence the quercetin antiproliferative and proapoptotic properties against HCC either alone and with the mentioned strategies; nevertheless, few investigations assessed specific activities on different processes related with cancer progression. Overall, further studies including animal models are needed to deeper investigate the precise mechanisms of action of quercetin as antitumor agent, as well as the potential of novel strategies aimed to improve quercetin effects in HCC.

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Section: Discussionmentioning

confidence: 95%

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

et al. 2019

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“…Our results indicated that changes in p16, p21, CDK2, and CDK4 protein levels seemed to make a major contribution to quercetin‐induced G 0 /G 1 arrest in HL‐60 cells. Accordingly, quercetin‐induced G 0 /G 1 cell cycle arrest was also observed in hepatoma cells, leukemic T cells, and breat cancer cells …”

Section: Discussionmentioning

confidence: 89%

Quercetin simultaneously induces G₀/G₁-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells

Chang

Chow

Chang

et al. 2017

Environmental Toxicology

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Quercetin is a plant-derived bioflavonoid with high anticancer activity in various tumors. Herein, the molecular mechanisms by which quercetin exerts its anticancer effects against HL-60 acute myeloid leukemia (AML) cells were investigated. Results showed that quercetin suppressed cell proliferation in the HL-60 cell line in vitro and in vivo. Quercetin-induced G /G -phase arrest occurred when expressions of cyclin-dependent kinase (CDK)2/4 were inhibited and the CDK inhibitors, p16 and p21, were induced. Moreover, quercetin treatment not only activated proapoptotic signaling like poly (ADP ribose) polymerase (PARP)-1 cleavage and caspase activation but also triggered autophagy events as shown by the increased expression of light chain 3 (LC3)-II, decreased expression of p62, and formation of acidic vesicular organelles. Interestingly, it was found that use of the autophagy inhibitor, 3-methyladenine, significantly enhanced quercetin-mediated apoptotic cell death as analyzed by MTS and DNA fragmentation assays. Moreover, pretreatment of HL-60 cells with the pan-caspase inhibitor, Z-VAD-fmk, dramatically reversed quercetin-mediated apoptotic and autophagic cell death. Although apoptosis and autophagy are two independent cell death pathways, our findings indicated that quercetin can activate caspases to trigger these two pathways, and both pathways played contrary roles in quercetin-mediated HL-60 cell death. In conclusion, besides promoting apoptosis, quercetin also induced cytoprotective autophagy in HL-60 cells, and inhibition of autophagy may be a novel strategy to enhance the anticancer activity of quercetin in AML.

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“…and MDAMB-231 cell line through the suppression of Twist via p38MAPK signaling pathway [14]. Genistein inhibits the growth of MDA-MB-231 by regulating the apoptosis related genes and up-regulation of Bax and p21WAF1 molecular pathways [15].…”

Section: Commentarymentioning

confidence: 99%

“…In-vitro studies using MDA-MB-231 cells showed that exposure to quercetin leads to an enhanced expression of Bax and cyt c release from mitochondrial membrane [13]. Quercetin also induces apoptosis in MCF-7and MDAMB-231 cell line through the suppression of Twist via p38MAPK signaling pathway [14]. Genistein inhibits the growth of MDA-MB-231 by regulating the apoptosis related genes and up-regulation of Bax and p21WAF1 molecular pathways [15].…”

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confidence: 99%

Flavonoids in Triple Negative Breast Cancer: Chemopreventive Phytonutrients

Tuli¹

2018

Arch Can Res

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CommentaryFlavonoids are phytochemicals that found in a variety of fruits and vegetables and known to possess anti-oxidant, antiinflammatory and anti-cancer properties [1,2]. It has been considered that flavonoids rich diet intake has promising role in human cancer prevention including breast cancer [3]. These phytonutrients have been traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast cancer [4,5]. According to epidemiological studies, breast cancer is the most common malignancies in women around the globe [6]. Breast cancer has heterogeneous nature with each of its subtype shown distinct morphological and clinical behavior [7]. Several factors including genetic, epigenetic and transcriptomic alterations are proved to be responsible for this diverse nature of breast cancer [8]. Among other subtypes triple negative breast cancer (TNBC) is highly aggressive form of breast cancer [9]. Statically TNBC alone comprises of 10%-17% of all breast carcinomas with incidence rate of 6%-28% of breast cancer [10]. Although, TNBC accounts for small proportion of all breast cancers, but has high mortality rate due to its aggressive nature. TNBC is characterized by the absence of estrogen receptors (ERs), progesterone receptors (PRs) and human epidermal growth factor receptor 2 (HER2) with normal breast tissue-like, and basal-like phenotype [10]. Lack of ERs, PRs and HER2 in TNBC makes it more difficult to treat [11]. Currently used hormonal or targeted therapies are only effective against those tumors that has either overexpressed receptors or transcriptional factors. Since neither receptors nor HER2 overexpression is occurred in TNBC therefore the therapies are found to be ineffective [11]. Interestingly, several in-vitro experiments determined the risk reducing effect of flavonoids in TNBC and suggesting them as a promising therapy.For example, Fisetin inhibited MDA-MB-468 and MDA-MB-231 cell's division and induced apoptosis involving mitochondrial membrane depolarization and activation of caspase-9 and caspase-8, as well as cleavage of PARP 1 [12]. Similarly, quercetin, another flavonoid compound also causees loss of membrane potential and activation of caspase cascade and PARP cleavage. In-vitro studies using MDA-MB-231 cells showed that exposure to quercetin leads to an enhanced expression of Bax and cyt c release from mitochondrial membrane [13]. Quercetin also induces apoptosis in MCF-7and MDAMB-231 cell line through the suppression of Twist via p38MAPK signaling pathway [14]. Genistein inhibits the growth of MDA-MB-231 by regulating the apoptosis related genes and up-regulation of Bax and p21WAF1 molecular pathways [15]. Study also found that genistein induced apoptosis in MDA-MB-231 cells by down-regulating Bcl-2 and up-regulating Bax, cleavage of caspase-3 along with inhibition of NF-κB activity via the MEK5/ERK5 pathway [16]. Furthermore, data demonstrated that genistein inhibited the growth of MDA-MB-231 cells by inhibiting NF-κB activity via the Nocth-1 sig...

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Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

Cited by 163 publications

References 38 publications

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

Quercetin simultaneously induces G₀/G₁-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells

Flavonoids in Triple Negative Breast Cancer: Chemopreventive Phytonutrients

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Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

Cited by 163 publications

References 38 publications

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

Quercetin simultaneously induces G0/G1-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells

Flavonoids in Triple Negative Breast Cancer: Chemopreventive Phytonutrients

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Quercetin simultaneously induces G₀/G₁-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells