Click synthesis of estradiol–cyclodextrin conjugates as cell compartment selective estrogens

Kim, Hye Yeong; Sohn, Jungwoo; Wijewickrama, Gihani T.; Edirisinghe, Praneeth D.; Gherezghiher, Teshome; Hemachandra, L. P. Madhubhani P.; Lu, Pei Yi; Chandrasena, R. Esala P.; Molloy, Mary Ellen; Tonetti, Debra A.; Thatcher, Gregory R. J.

doi:10.1016/j.bmc.2009.11.046

Cited by 30 publications

(13 citation statements)

References 59 publications

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“…The classical actions of ER as a nuclear receptor and transcription factor have been differentiated from nonclassical activity by use of commercially available, membrane impermeable probes, such as E 2 -BSA (46 -48). Extended incubation of E 2 -BSA in cell culture leads to degradation to BSA and E 2 ; therefore, the E 2 conjugate, 7EqCD, a stable, extranuclear ER agonist was also employed (30,47). Both 7EqCD (Fig.…”

Section: Effects Of Estrogens and Antiestrogens In Presence Of Nos Blmentioning

confidence: 99%

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

et al. 2010

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Estrogen action, via both nuclear and extranuclear estrogen receptors (ERs), induces a variety of cellular signals that are prosurvival or proliferative, whereas nitric oxide (NO) can inhibit apoptosis via caspase S-nitrosylation and via activation of soluble guanylyl cyclase to produce cGMP. The action of 17β-estradiol (E(2)) at ER is known to elicit NO signaling via activation of NO synthase (NOS) in many tissues. The MCF-10A nontumorigenic, mammary epithelial cell line is genetically stable and insensitive to estrogenic proliferation. In this cell line, estrogens or NOS inhibitors alone had no significant effect, whereas in combination, apoptosis was induced rapidly in the absence of serum; the presence of inducible NOS was confirmed by proteomic analysis. The application of pharmacological agents determined that apoptosis was dependent upon NO/cGMP signaling via cyclic GMP (cGMP)-dependent protein kinase and could be replicated by inhibition of the phosphatidylinositol 3 kinase/serine-threonine kinase pathway prior to addition of E(2). Apoptosis was confirmed by nuclear staining and increased caspase-3 activity in E(2) + NOS inhibitor-treated cells. Apoptosis was partially inhibited by a pure ER antagonist and replicated by agonists selective for extranuclear ER. Cells were rescued from E(2)-induced apoptosis after NOS blockade, by NO-donors and cGMP pathway agonists; preincubation with NO donors was required. The NOS and ER status of breast cancer tissues is significant in etiology, prognosis, and therapy. In this study, apoptosis of preneoplastic mammary epithelial cells was triggered by estrogens via a rapid, extranuclear ER-mediated response, after removal of an antiapoptotic NO/cGMP/cGMP-dependent protein kinase signal.

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Section: Effects Of Estrogens and Antiestrogens In Presence Of Nos Blmentioning

confidence: 99%

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

et al. 2010

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“…4 In addition to the synthetic advantages, CCCs have unique, structural characteristics including well-defined structures, precise molecular weights, and multivalent functionalization sites. CCCs have been extensively exploited in polymers, 5,6 nucleic acid carriers, 7-9 sensors, 10 glycoconjugates, 11-13 multivalent scaffolds, [14][15][16] and magnetic resonance imaging probes. 17,18 Several CDs are used industrially in pharmaceutical and allied applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Cytotoxicity, and Phase-Solubility Study of Cyclodextrin Click Clusters

Lê

Jeon

Lim

et al. 2014

Journal of Pharmaceutical Sciences

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“…Exploiting this concept, Thatcher et al studied the synthesis and biological applications of estradiol‐CD conjugates as extranuclear selective estrogens 55. In this case, two synthetic routes were tested (amino linkage and triazole linkage, Scheme ).…”

Section: A Powerful Combination In Life Sciencementioning

confidence: 99%

When Cyclodextrins Meet Click Chemistry

et al. 2012

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International audienceCyclodextrins are important building blocks in organic chemistry. This review deals with the role of click chemistry in this family of cyclic oligosaccharides, focusing on the different areas of chemistry, including chromatography, biological applications, the elaboration of superstructures, and metal detection, that benefit from this reaction. In this paper, attention is given to organic modifications by using functionalizations such as azidation and propargylation and to click chemistry grafting onto the two faces of cyclodextrins. Research papers where cyclodextrins are not directly involved in a click chemistry reaction are not considered

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Click synthesis of estradiol–cyclodextrin conjugates as cell compartment selective estrogens

Cited by 30 publications

References 59 publications

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

Synthesis, Cytotoxicity, and Phase-Solubility Study of Cyclodextrin Click Clusters

When Cyclodextrins Meet Click Chemistry

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