We are analyzing https://link.springer.com/article/10.1186/bcr2208.

Title:
Buthionine sulfoximine sensitizes antihormone-resistant human breast cancer cells to estrogen-induced apoptosis | Breast Cancer Research
Description:
Introduction Estrogen deprivation using aromatase inhibitors is one of the standard treatments for postmenopausal women with estrogen receptor (ER)-positive breast cancer. However, one of the consequences of prolonged estrogen suppression is acquired drug resistance. Our group is interested in studying antihormone resistance and has previously reported the development of an estrogen deprived human breast cancer cell line, MCF-7:5C, which undergoes apoptosis in the presence of estradiol. In contrast, another estrogen deprived cell line, MCF-7:2A, appears to have elevated levels of glutathione (GSH) and is resistant to estradiol-induced apoptosis. In the present study, we evaluated whether buthionine sulfoximine (BSO), a potent inhibitor of glutathione (GSH) synthesis, is capable of sensitizing antihormone resistant MCF-7:2A cells to estradiol-induced apoptosis. Methods Estrogen deprived MCF-7:2A cells were treated with 1 nM 17β-estradiol (E2), 100 μM BSO, or 1 nM E2 + 100 μM BSO combination in vitro, and the effects of these agents on cell growth and apoptosis were evaluated by DNA quantitation assay and annexin V and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. The in vitro results of the MCF-7:2A cell line were further confirmed in vivo in a mouse xenograft model. Results Exposure of MCF-7:2A cells to 1 nM E2 plus 100 μM BSO combination for 48 to 96 h produced a sevenfold increase in apoptosis whereas the individual treatments had no significant effect on growth. Induction of apoptosis by the combination treatment of E2 plus BSO was evidenced by changes in Bcl-2 and Bax expression. The combination treatment also markedly increased phosphorylated c-Jun N-terminal kinase (JNK) levels in MCF-7:2A cells and blockade of the JNK pathway attenuated the apoptotic effect of E2 plus BSO. Our in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of BSO either as a single agent or in combination with E2 significantly reduced tumor growth of MCF-7:2A cells. Conclusions Our data indicates that GSH participates in retarding apoptosis in antihormone-resistant human breast cancer cells and that depletion of this molecule by BSO may be critical in predisposing resistant cells to E2-induced apoptotic cell death. We suggest that these data may form the basis of improving therapeutic strategies for the treatment of antihormone resistant ER-positive breast cancer.
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cells, bso, mcfa, apoptosis, estradiol, cancer, glutathione, pubmed, article, cell, breast, treatment, bcl, google, scholar, cas, control, figure, compared, estrogen, levels, apoptotic, effect, mcf, mitochondrial, usa, treated, growth, protein, gsh, jnk, group, death, sulfoximine, combination, performed, tumor, data, human, resistant, expression, days, resistance, estradiolinduced, pathway, buthionine, staining, shown, analysis, significantly,

Topics {✒️}

c-jun n-terminal kinase c-jun nh2-terminal kinase n-2-hydroxyethylpiperazine-n'-2-ethanesulfonic acid pan-caspase inhibitor z-vad thiol-mediated redox regulation n-terminal activation domain jnk substrate phospho-c-jun article download pdf c-jun/jnk signaling pathway stress-activated protein kinase nonsteroidal flavone-methanesulfonate derivatives heat stress-induced perturbations estrogen-free rpmi media water-soluble tripeptide composed real-time quantitative pcr quantitative real-time pcr cellular oxidation-reduction potential transcription factor c-jun mitogen-activated protein kinases anti-fluorescein antibody conjugated long-term estrogen deprivation o'dwyer pj metastatic breast cancer death receptors fasr/fasl bso-mediated estradiol-induced apoptosis oxford biomedical research intravenous l-buthionine sulfoximine ncr-foxn1nu athymic mice selective estrogen-receptor modulators c-jun/jnk pathway low-dose estrogen therapy positive breast cancer paraffin-embedded tumor sections cross-sectional tumor area significant time-dependent decrease sensitizes tumor cells advanced breast cancer bcl-xl inhibit apoptosis wild-type mcf-7 cells annexin v-positive cells annexin v-fluorescein isothiocyanate antihormone resistant cells article lewis-wambi anti-cox iv antibody clin breast cancer bcl-xl protein levels high-dose estrogen treatment phosphorylated c-jun cellular redox state annexin v-propidium iodide

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Karnofsky lecture: the paradoxical actions of estrogen in breast cancer – survival or death?

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         Surgical Oncology
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      name:Department of Pathology, Fox Chase Cancer Center, Philadelphia, USA
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