scholarly journals Thapsigargin, inhibitor of sarco-endoplasmic Ca2+-ATPase, effectively suppresses the expression of S100A4 in human breast cancer cell line

2019 ◽  
Vol 486 (2) ◽  
pp. 255-257
Author(s):  
A. P. Kotnova ◽  
B. M. Lyanova ◽  
E. A. Dukhanina ◽  
T. N. Portseva ◽  
Yu. V. Ilyin ◽  
...  

Thapsigargin, the SERCA ATPase inhibitor, effectively suppresses the expression of metastasis marker S100A4 in breast cancer cells MDA-MB231. It has been demonstrated that transcription of the S100A4 gene is controlled by Ca2+-signaling pathways. It has been shown that synthesis of S100A4 mRNA and protein in the MDA-MB231 cell line is effectively inhibited by thapsigargin at a concentration of 0.4-4 µM, while preserving cell survival. We assume that a change in gene transcription in response to the disruption of Ca2+ homeostasis plays a direct role in the remodeling of Ca2+-signaling pathways.

2018 ◽  
Vol 18 (17) ◽  
pp. 1465-1474 ◽  
Author(s):  
Jessica R. Branco ◽  
Vanessa G. Oliveira ◽  
Amanda M. Esteves ◽  
Ingrid C. Chipoline ◽  
Miriam F.O. Lima ◽  
...  

Background: Breast cancer is a major cause of death among women worldwide. Treatment for breast cancer involves the surgical removal of cancer tissue, followed by chemotherapy. Although the treatment is efficient, especially when the cancer is detected early, recurrence is common and is often resistant to the previous treatment. Therefore, a constant search for efficient and novel drugs for the treatment of breast cancer is mandatory. Recently, triazole derivatives have shown promising effects against different types of cancer, revealing these molecules as putative anticancer drugs. Experimental: We have synthesized a series of naphthotriazolyl-4-oxoquinoline derivatives and tested their activity against a human breast cancer cell line. Among the compounds tested, we identified a molecule that killed the human breast cancer cell line MCF-7 with minimal effects on its noncancer counterpart, MCF10A. This effect was seen after 24 hours of treatment and persisted for additional 24 hours after treatment withdrawal. After 1 hour of treatment, the compound, here named 12c, promoted a decrease in cell glucose consumption and lactate production. Moreover, the cells treated with 12c for 1 hour showed diminished intracellular ATP levels with unaltered mitochondrial potential and increased reactive oxygen species production. Additionally, apoptosis was triggered after treatment with the drug for 1 hour. All of these effects are only observed with MCF-7 cells, and not MCF10A. These data show that 12c has selective activity against breast cancer cells and is a potential candidate for a novel anticancer drug. Results and Conclusion: The naphthotriazolyl-4-oxoquinoline derivatives were obtained in good to moderate yields, and one of them, 12c, exhibited strong and selective antitumor properties. The antitumor mechanism involves inhibition of glycolysis, diminished intracellular ATP levels, induction of ROS production and triggering of apoptosis. These effects are all selective for cancer cells, since noncancer cells are unaffected, and these effects can only be attributed to the whole molecule, as different pharmacophoric groups did not reproduce these effects.


2006 ◽  
Vol 26 (17) ◽  
pp. 6412-6424 ◽  
Author(s):  
Rebecca S. Muraoka-Cook ◽  
Laura S. Caskey ◽  
Melissa A. Sandahl ◽  
Debra M. Hunter ◽  
Carty Husted ◽  
...  

ABSTRACT HER4 expression in human breast cancers correlates with a positive prognosis. While heregulin inhibits the growth of HER4-positive breast cancer cells, it does so by undefined mechanisms. We demonstrate that heregulin-induced HER4 activity inhibits cell proliferation and delays G2/M progression of breast cancer cells. While investigating pathways of G2/M delay, we noted that heregulin increased the expression of BRCA1 in a HER4-dependent, HER2-independent manner. Induction of BRCA1 by HER4 occurred independently of the cell cycle. Moreover, BRCA1 expression was elevated in HER4-postive human breast cancer specimens. Heregulin stimulated c-Jun N-terminal kinase (JNK), and pharmacologic inhibition of JNK impaired heregulin-enhanced expression of BRCA1 and mitotic delay; inhibition of Erk1/2 did not. Knockdown of BRCA1 with small interfering RNA in a human breast cancer cell line interfered with HER4-mediated mitotic delay. Heregulin/HER4-dependent mitotic delay was examined further with an isogenic pair of mouse mammary epithelial cells (MECs) derived from mice harboring homozygous LoxP sites flanking exon 11 of BRCA1, such that one cell line expressed BRCA1 while the other cell line, after Cre-mediated excision, did not. BRCA1-positive MECs displayed heregulin-dependent mitotic delay; however, the isogenic BRCA1-negative MECs did not. These results suggest that heregulin-mediated growth inhibition in HER4-postive breast cancer cells requires BRCA1.


2014 ◽  
Vol 229 ◽  
pp. S153-S154
Author(s):  
Noelia Miret ◽  
Carolina Pontillo ◽  
Florencia Chiappini ◽  
Laura Alvarez ◽  
Diana Kleiman de Pisarev ◽  
...  

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


2003 ◽  
Vol 278 (44) ◽  
pp. 43363-43372 ◽  
Author(s):  
Jun Kawagoe ◽  
Masahide Ohmichi ◽  
Toshifumi Takahashi ◽  
Chika Ohshima ◽  
Seiji Mabuchi ◽  
...  

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