Apigenin-induced-apoptosis is mediated by the activation of PKCδ and caspases in leukemia cells

Vargo, Melissa A.; Voß, Oliver; Poustka, Frantisek; Cardounel, Arturo J.; Grotewold, Erich; Doseff, Andrea I.

doi:10.1016/j.bcp.2006.06.010

Cited by 146 publications

(139 citation statements)

References 42 publications

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“…For example, apigenin has been shown previously to induce cell cycle arrest in cultured cells (Reiners et al, 1999). In addition, apigenin has been reported to induce apoptosis by activating protein kinase C␦ and caspases in different cell lines (Khan and Sultana, 2006;Vargo et al, 2006). The data shown in the current study indicate that the modified form of apigenin, Apigenin-Protac, lacks the ability to both significantly induce CYP1A1 and CYP1B1 expression (Fig.…”

Section: A P I G E N I N -P R O T a C A P I G E N I N -P R O T A C + mentioning

confidence: 54%

Development of an Aryl Hydrocarbon Receptor Antagonist Using the Proteolysis-Targeting Chimeric Molecules Approach: A Potential Tool for Chemoprevention

Puppala

Lee²,

Kim³

et al. 2008

Mol Pharmacol

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Activation of the aryl hydrocarbon receptor (AHR) by agonists and environmental contaminants like dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) leads to many adverse biological effects, including tumor promotion. With this in mind, we propose that agents that block the AHR pathway may be therapeutically beneficial, particularly by exhibiting chemopreventive activities. In our current research, we have focused on the development of an AHR antagonist using a chemical genetic approach called PROTACS (PROteolysis-TArgeting Chimeric moleculeS). PROTACS is a novel approach of tagging small recognition sequences of a specific E3 ubiquitin ligase complex to a known ligand for the receptor of interest (AHR) for targeting its degradation. Here, we present the design and initial characterization of AHR targeting PROTACS (ApigeninProtac) designed to degrade and inhibit the AHR in epithelial cells. Our results demonstrate the "proof of concept" of this approach in effectively blocking AHR activity in cultured cells.Exposures to environmental factors are believed to play a substantial role in the development of many human cancers

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Section: A P I G E N I N -P R O T a C A P I G E N I N -P R O T A C + mentioning

confidence: 54%

Development of an Aryl Hydrocarbon Receptor Antagonist Using the Proteolysis-Targeting Chimeric Molecules Approach: A Potential Tool for Chemoprevention

Puppala

Lee²,

Kim³

et al. 2008

Mol Pharmacol

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“…Apoptosis is also induced by other tumor growthinhibiting phytochemicals [32] and anticancer drugs such as 5-flurouracil [33] and cisplatin [34]. Previous studies demonstrating induction of apoptosis by apigenin suggested that the following mechanisms may be involved: induction of caspase 3 [35], induction/activation of p53 [36], up-regulation of FADD [31], and, in MDA-MB-435 cells, stimulation of proteasome-dependent degradation of Her2/neu [27]. In the present study apigenin was associated with reduced tumor cell Her2/neu immunoreactivity, though in agreement with a previous report [27], apigenin did not reduce Her2/neu mRNA levels (not shown).…”

Section: Discussionmentioning

confidence: 99%

Apigenin Induces Apoptosis and Blocks Growth of Medroxyprogesterone Acetate-Dependent BT-474 Xenograft Tumors

et al. 2012

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Recent clinical and epidemiological evidence shows that hormone replacement therapy (HRT) containing both estrogen and progestin increases the risk of primary and metastatic breast cancer in post-menopausal women while HRT containing only estrogen does not. We and others previously showed that progestins promote the growth of human breast cancer cells in vitro and in vivo. In this study, we sought to determine whether apigenin, a low molecular weight anticarcinogenic flavonoid, inhibits the growth of aggressive Her2/neu-positive BT-474 xenograft tumors in nude mice exposed to medroxyprogesterone acetate (MPA), the most commonly used progestin in the USA. Our data clearly show that apigenin (50 mg/kg) inhibits progression and development of these xenograft tumors by inducing apoptosis, inhibiting cell proliferation, and reducing expression of Her2/neu. Moreover, apigenin reduced levels of vascular endothelial growth factor (VEGF) without altering blood vessel density, indicating that continued expression of VEGF may be required to promote tumor cell survival and maintain blood flow. While previous studies showed that MPA induces receptor activator of nuclear factor kappa-B ligand (RANKL) expression in rodent mammary gland, MPA reduced levels of RANKL in human tumor xenografts. RANKL levels remained suppressed in the presence of apigenin. Exposure of BT-474 cells to MPA in vitro also resulted in lower levels of RANKL; an effect that was independent of progesterone receptors since it occurred both in the presence and absence of the antiprogestin RU-486. In contrast to our in vivo observations, apigenin protected against MPA-dependent RANKL loss in vitro, suggesting that MPA and apigenin modulate RANKL levels differently in breast cancer cells in vivo and in vitro. These preclinical findings suggest that apigenin has potential as an agent for the treatment of progestin-dependent breast disease.

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“…The fluorescence provided by the ring-stacking interaction of flavonol and flavone aglycones with diphenylboric acid (DPBA) has been utilized to investigate the localization of several flavonoids (Buer and Muday, 2004;Peer and Murphy, 2006;Vargo et al, 2006;Hsieh and Huang, 2007). However, DPBA does not fluoresce with anthocyanins, prompting us to seek another means for cytoplasmic visualization of these compounds.…”

Section: Novel Fluorescent Properties Of Arabidopsis Anthocyaninsmentioning

confidence: 99%

A Trafficking Pathway for Anthocyanins Overlaps with the Endoplasmic Reticulum-to-Vacuole Protein-Sorting Route in Arabidopsis and Contributes to the Formation of Vacuolar Inclusions

Poustka¹,

Irani²,

Feller³

et al. 2007

Plant Physiology

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Plants produce a very large number of specialized compounds that must be transported from their site of synthesis to the sites of storage or disposal. Anthocyanin accumulation has provided a powerful system to elucidate the molecular and cellular mechanisms associated with the intracellular trafficking of phytochemicals. Benefiting from the unique fluorescent properties of anthocyanins, we show here that in Arabidopsis (Arabidopsis thaliana), one route for anthocyanin transport to the vacuole involves vesicle-like structures shared with components of the secretory pathway. By colocalizing the red fluorescence of the anthocyanins with green fluorescent protein markers of the endomembrane system in Arabidopsis seedlings, we show that anthocyanins are also sequestered to the endoplasmic reticulum and to endoplasmic reticulum-derived vesicle-like structures targeted directly to the protein storage vacuole in a Golgi-independent manner. Moreover, our results indicate that vacuolar accumulation of anthocyanins does not depend solely on glutathione S-transferase activity or ATP-dependent transport mechanisms. Indeed, we observed a dramatic increase of anthocyanin-filled subvacuolar structures, without a significant effect on total anthocyanin levels, when we inhibited glutathione S-transferase activity, or the ATP-dependent transporters with vanadate, a general ATPase inhibitor. Taken together, these results provide evidence for an alternative novel mechanism of vesicular transport and vacuolar sequestration of anthocyanins in Arabidopsis.

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Apigenin-induced-apoptosis is mediated by the activation of PKCδ and caspases in leukemia cells

Cited by 146 publications

References 42 publications

Development of an Aryl Hydrocarbon Receptor Antagonist Using the Proteolysis-Targeting Chimeric Molecules Approach: A Potential Tool for Chemoprevention

Development of an Aryl Hydrocarbon Receptor Antagonist Using the Proteolysis-Targeting Chimeric Molecules Approach: A Potential Tool for Chemoprevention

Apigenin Induces Apoptosis and Blocks Growth of Medroxyprogesterone Acetate-Dependent BT-474 Xenograft Tumors

A Trafficking Pathway for Anthocyanins Overlaps with the Endoplasmic Reticulum-to-Vacuole Protein-Sorting Route in Arabidopsis and Contributes to the Formation of Vacuolar Inclusions

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