scholarly journals Protein expression pattern in response to ionizing radiation in MCF-7 human breast cancer cells

2011 ◽  
Vol 3 (1) ◽  
pp. 147-154 ◽  
Author(s):  
SAMIL JUNG ◽  
SOONDUCK LEE ◽  
JAYHEE LEE ◽  
CHENGPING LI ◽  
JI-YEON OHK ◽  
...  
2001 ◽  
Vol 155 (4) ◽  
pp. 543-553 ◽  
Author(s):  
Zhongkui Li ◽  
Liqun Xia ◽  
Leo M. Lee ◽  
Alexander Khaletskiy ◽  
Jianyi Wang ◽  
...  

2020 ◽  
Author(s):  
Azubuike P. Ebokaiwe ◽  
Ting Peng ◽  
Emmanuel M. Njoya ◽  
Zongyuan Zhou ◽  
Ahmed A. Hussein ◽  
...  

Abstract Background: Loranthus micranthus (African mistletoe) is a woody parasitic plant. It is found in Africa, Asia, Europe, and America. Its leaves and stem/twigs have been used in traditional medicine in various continents for the treatment of metabolic diseases: diabetes, hypertension, and cancer. The present study is designed to investigate the effect of Loranthus micranthus leaves and stem (LML and LMS) extracts on indoleamine 2,3-dioxygenase (IDO); a key regulator of cancer immunity; and the possible molecular mechanism(s) involved.Methods: Human breast cancer cells; MDA MB-231 and MCF-7 were pre-treated with LML and LMS at doses of 1-30µg/mL for 2 hours. This was followed by interferon-γ (INF-γ) stimulation at 50 ng/mL for 24 hours. After the treatment period, the activity of indoleamine 2,3 dioxygenase 1 (IDO-1) and T cell proliferation were determined using a spectrophotometric assay. Protein expression of IDO-1, IDO-2, tryptophan-2,3-dioxygenase-2 (TDO-2), Bridging inhibitor 1 (BIN-1), Janus kinase/signal transducers and activators of transcription (JAK/STAT), Inhibitor of κ B (IκBα) and Nuclear factor-κB (NF-κB) pathway were analyzed using the western blotting technique. The mRNA expression of IDO-1 was quantified using the qRT-PCR technique. Results: MDA MB-231 and MCF-7 cells pre-treated with LML and LMS exhibited lower kynurenine synthesis than that of INF-γ treatment. We observed downregulation of IDO-1, IDO-2, and TDO-2 protein expressions, and lower IDO-1 catalytic activity in LML and LMS pretreated cells than those of INF-γ treated cells alone. Cells pretreated with LML and LMS exhibited significant downregulation of phosphorylation of JAK-1, JAK-2, STAT-1, and STAT-3 than those of IFN-γ treatment alone. Furthermore, LML and LMS pre-treated cells exhibited upregulation of IκBα and BIN-1 protein expression compared with IFN-γ treated cells alone. Additionally, LML and LMS pretreatment significantly improved T cell viability when compared with IFN-γ treated cells alone. Conclusion: These findings indicate that LML and LMS extracts regulate immune responses in cancer cells by inhibiting IDO activity/expression in a JAK/STAT and NF-κB-dependent manner. This accounts for their anticancer effects in traditional medicine, hence a promising candidate for future drug development.


2003 ◽  
Vol 17 (10) ◽  
pp. 2002-2012 ◽  
Author(s):  
Olga A. Sukocheva ◽  
Lijun Wang ◽  
Nathaniel Albanese ◽  
Stuart M. Pitson ◽  
Mathew A. Vadas ◽  
...  

Abstract Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.


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