Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer

Nelson, Nadine; Szekeres, Karoly; Iclozan, Cristina; Rivera, Ivannie Ortiz; McGill, Andrew R.; Johnson, Gbemisola; Nwogu, Onyekachi; Ghansah, Tomar

doi:10.1371/journal.pone.0170197

Cited by 40 publications

(43 citation statements)

References 55 publications

(73 reference statements)

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“…The decrease in Ikaros expression causes a reduction in the CD4+ and CD8+ T cell expression, and an increase in CD4+ CD25+ Tregs in tumor-bearing mice. In pancreatic cancer cells, CK2 regulates Ikaros expression, and apigenin has shown to stabilize Ikaros by downregulating CK2 to central T cell homeostasis [118]. …”

Section: 0 Effect Of Apigenin In Various Human Cancersmentioning

confidence: 99%

Plant Flavone Apigenin: an Emerging Anticancer Agent

et al. 2017

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Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

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“…In order to confirm that CK2 inhibition attenuates oxytocin‐induced contractions, we used another selective inhibitor of CK2, apigenin (Nelson et al., ). Apigenin at the same concentration (50 μ m ) inhibited the oxytocin response in the late pregnant uterine strips in a similar manner.…”

Section: Discussionmentioning

confidence: 99%

Casein kinase 2 inhibition impairs spontaneous and oxytocin-induced contractions in late pregnant mouse uterus

et al. 2018

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The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin-induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX-4945 elicited a concentration-dependent relaxation in late pregnant mouse uterus. CX-4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin-induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F response, but CX-4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin-induced uterine contractions in the late pregnant mouse.

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“…CK2 also phosphorylates key proteins that possess anti-apoptotic functions, thus suppressing cellular apoptosis (Gray et al, 2014). The ability of CK2 to override cellular apoptotic signaling suggests a role in tumorigenesis and CK2 has been shown to aggressively increase tumor growth in most, if not all, cancer cells tested thus far (Guerra and Issinger, 1999; Meggio and Pinna, 2003; Nelson et al, 2017). …”

Section: Casein Kinase II (Ck2)mentioning

confidence: 99%

Casein Kinase II (CK2), Glycogen Synthase Kinase-3 (GSK-3) and Ikaros mediated regulation of leukemia

Gowda

Soliman

Kapadia

et al. 2017

Advances in Biological Regulation

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Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN. More recent data demonstrate another mechanism through which CK2 promotes the PI3K pathway – via transcriptional regulation of PI3K pathway genes by the newly-discovered CK2-Ikaros axis. Together, these data suggest that the CK2 and GSK-3 pathways regulate AKT/PI3K signaling in leukemia via two complementary mechanisms: a) direct phosphorylation of PTEN and b) transcriptional regulation of PI3K-promoting genes. Functional interactions between CK2, Ikaros and GSK3 define a novel signaling network that regulates proliferation of leukemia cells. This regulatory network involves both direct posttranslational modifications (by CK and GSK-3) and transcriptional regulation (via CK2-mediated phosphorylation of Ikaros). This information provides a basis for the development of targeted therapy for leukemia.

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“…Cardenas reported that apigenin suppressed leukocyte infiltration by reducing the activation of NF-kB [16]. And, Nelson group showed that apigenin recovered T cell homeostasis and function by increasing the expression of Ikaros in murine pancreatic cancer [17].…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis

Lee¹,

Cho²

2019

Microbiology and Biotechnology Letters

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“…Literature describes both studies that have determinates API potential in in vitro cell cultures, whereas others in in vivo animal models. Experimental animal models employing the fallowing cell lines : breast cancer (MCF-7), colon cancer (Caco-2), lung cancer (B16-BL6 murine melanoma cells), pancreatic cancer (PaCC), melanoma cancer (A375), hepatocellular carcinoma (HCC) were designed in order to evaluate the chemopreventive property of this phytocompound [15][16][17][18][19].An increased number of studies assign the cancer preventive effect of API to its antiinflammatory and antioxidant properties [20]. Studies on the topic have shown that in vitro it has antiproliferative and/or pro-apoptotic role against various cancer cell lines including: prostate cancer (PC-3 and DU145), hematologic cancer (HL-60), ovarian cancer (HO-8910PM), liver cancer (HeLa), lung cancer B16-BL6 murine melanoma cells) and breast cancer (MCF7).…”

mentioning

confidence: 99%

An in vitro Evaluation of Apigenin and Apigenin-7-O-glucoside Against HeLa Human Cervical Cancer Cell Line

Minda¹,

Avram²,

Pavel³

et al. 2020

Rev. Chim.

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pigenin (API) is a phytocompound belonging to the subclass of flavones that can be found in both functional foods as well as medicinal plants. Recent studies have assigned API antioxidant, anti-inflammatory, anti-spasmodic, anti-viral, anti-thrombotic, anti-angiogenic and chemopreventive potential in vitro on various cell lines and/or in experimental animal models. Apigenin-7-O-glucoside (API-7) is one of its main glycosides and can be commonly found in chamomile flowers, parsley, celery. The aim of this study was to evaluate the in vitro anti-proliferative and pro-apoptotic effects of API and its glycoside (apigenin-7-O-glucoside) against HeLa human cervical cancer cells. Results have shown that in the set experimental conditions both the aglycone as well as the heteroside elicit antiproliferative and pro-apoptotic potential against the screened cell line, the aglycone being more active than the heteroside.

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Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer

Cited by 40 publications

References 55 publications

Plant Flavone Apigenin: an Emerging Anticancer Agent

Casein kinase 2 inhibition impairs spontaneous and oxytocin-induced contractions in late pregnant mouse uterus

Casein Kinase II (CK2), Glycogen Synthase Kinase-3 (GSK-3) and Ikaros mediated regulation of leukemia

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis

An in vitro Evaluation of Apigenin and Apigenin-7-O-glucoside Against HeLa Human Cervical Cancer Cell Line

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