Journals / Pamukkale Tıp Dergisi / 2020 / Cilt: 13 - Sayı: 1

The effect of DEBIO 1143 usage alone or in combination with Tamoxifen on estrogen receptor positive breast cancer cell lines.

DEBIO 1143’ün tek başına veya tamoksifenle kombinasyonunun östrojen reseptörü pozitif meme kanseri hücre hatlarındaki etkisi.

Pages
9–18
Publication Date
2020-01-21
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Further research is needed to determine which cell death type other than apoptosis is associated with a reduction in cell viability caused by combined administration.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Purpose: To investigate the effect of increased concentrations of Tamoxifen (TAM) and DEBIO 1143 (AT-406) administered alone or in combination on cells in MCF-7 and BT-474 estrogen receptor positive (ER +) breast cancer cell lines.Materials and Methods: The effect of Tamoxifen and DEBIO 1143 administered alone or in combination on cell viability in MCF-7 and BT-474 cell lines at the 72nd hour was assessed by the XTT test.
📊
Key Findings & Data:Multi-parameter apoptosis assay kit was used to display the effect of the alone/combination of TAM and DEBIO 1143 on both cell lines.
💡
Conclusion & Impact:Further research is needed to determine which cell death type other than apoptosis is associated with a reduction in cell viability caused by combined administration.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:DEBIO 1143 · ER + meme kanseri · SMAC mimetik

Abstract

Purpose: To investigate the effect of increased concentrations of Tamoxifen (TAM) and DEBIO 1143 (AT-406) administered alone or in combination on cells in MCF-7 and BT-474 estrogen receptor positive (ER +) breast cancer cell lines.Materials and Methods: The effect of Tamoxifen and DEBIO 1143 administered alone or in combination on cell viability in MCF-7 and BT-474 cell lines at the 72nd hour was assessed by the XTT test. Multi-parameter apoptosis assay kit was used to display the effect of the alone/combination of TAM and DEBIO 1143 on both cell lines. Fluorescence microscobic analysis was performed. Results: The IC50 value of TAM was 3.8±0.6 micromolar (µM) and 18.9±6.7 µM in the MCF-7 and BT-474 cell lines, respectively. The IC50 value of DEBIO 1143 was 15±0.5 µM in the MCF-7 cell line. The results related to drug combination were statistically significant for both cell lines (p<0.001). The decrease in cell viability was not associated with apoptosis.Conclusion: In ER + breast cancer cell lines, the combined doses of the TAM and DEBIO 1143 reduced cell viability more than their administration alone. Combined administrations in both cell lines were concluded in a synergistic effect. Further research is needed to determine which cell death type other than apoptosis is associated with a reduction in cell viability caused by combined administration.

Özet

Amaç: Tamoxifen (TAM) ve DEBIO 1143 (AT-406)’ün artan konsantrasyonlarının tek başına veya birlikte uygulanmasının, MCF-7 ve BT-474 östrojen reseptörü pozitif (ER+) meme kanseri hücre hatlarındaki etkisini araştırmak.Gereç ve Yöntem: XTT testi, Tamoxifen ve DEBIO 1143’ün tek başına veya birlikte kullanımın 72 saatlik MCF-7 ve BT-474 hücre hatlarındaki hücre canlılığı üzerine olan etkisini belirlemek için kullanıldı. TAM ve DEBIO 1143'ün tek başına / kombinasyonunun her iki hücre hattı üzerindeki etkisini göstermek için çok parametreli apoptoz analiz kiti kullanıldı ve floresan mikroskobik görüntüleme yapıldı. Bulgular: TAM'ın IC50 değeri MCF-7 ve BT-474 hücre hatlarında sırasıyla 3,8±0,6 mikromolar (µM) ve 18,9±6,7 µM idi. DEBIO 1143'ün IC50 değeri, MCF-7 hücre hattında 15±0,5 uM idi. İlaç kombinasyonuna bağlı sonuçlar her iki hücre hattı için istatistiksel olarak anlamlıydı (p<0,001). Hücre canlılığının azalması apoptozis ile ilişkili bulunmadı. Sonuç: ER+ meme kanseri hücre hatlarında, kombinasyon halinde uygulanan TAM ve DEBIO 1143 dozlarının, tek başına uygulanmalarına göre hücre canlılığını daha fazla azalttığı belirlenmiştir. Her iki hücre hattında kombinasyon dozlarının uygulanması sinerjik bir etki göstermiştir. Kombine uygulamanın sebep olduğu hücre canlılığındaki azalmanın, apoptoz dışındaki hangi hücre ölüm tipi ile olduğunu belirlemek için ileri araştırmalara ihtiyaç vardır.

🔖

Cite This Article

TUĞRUL, B., İŞSEVEN, M. (2020). The effect of DEBIO 1143 usage alone or in combination with Tamoxifen on estrogen receptor positive breast cancer cell lines.. Pamukkale Tıp Dergisi, Cilt: 13 - Sayı: 1, 9–18. https://ajindex.com/articles/696487

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (11)

  1. Abotaleb M, Kubatka P, Caprnda M, et al. Chemotherapeutic agents for the treatment of metastatic breast cancer: an update. Biomed Pharmacother 2018 May;101:458-477. doi: 10.1016/j.biopha.2018.02.108
  2. Chen B, Wang Y, Kane SE, Chen S. Improvement of sensitivity to tamoxifen in estrogen receptor-positive and Herceptin-resistant breast cancer cells. J Mol Endocrinol 2008 Nov;41(5):367-377. doi: 10.1677/JME-08-0026
  3. Sun H, Nikolovska-Coleska Z, Yang CY, et al. Design of small-molecule peptidic and nonpeptidic Smac mimetics. Acc Chem Res 2008 Oct;41(10):1264-1277. doi: 10.1021/ar8000553
  4. Brunckhorst MK, Lerner D, Wang S, Yu Q. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. Cancer Biol Ther 2012 Jul;13(9):804-811. 5.Tuğrul B, İşseven M. SMAC mimetiği olarak AT-406’nın kanserdeki rolü (Role of AT-406 as a SMAC mimetic in cancer). Akd Med J 2018;2:114-119. doi: 10.17954/amj.2018.132
  5. Subik K, Lee JF, Baxter L, et al. The expression patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by immunohistochemical analysis in breast cancer cell lines. Breast Cancer (Auckl) 2010 May 20;4:35-41. Erratum in: Breast Cancer (Auckl) 2018 Oct 16;12:1178223418806626. PubMed PMID: 20697531
  6. Lasfargues EY, Coutinho WG, Redfield ES. Isolation of two human tumor epithelial cell lines from solid breast carcinomas. J Natl Cancer Inst 1978 Oct;61(4):967-978. PubMed PMID: 212572
  7. Karami-Tehrani F, Salami S. Cell kinetic study of tamoxifen treated MCF-7 and MDA-MB 468 breast cancer cell lines Iranian Biomedical Journal 2003;7(2):51-56
  8. Wang C, Wu P, Shi JF, Jiang ZH, Wei XY. Synthesis and cancer cell growth inhibitory activity of icaritin derivatives. Eur J Med Chem 2015 Jul 15;100:139-150. doi: 10.1016/j.ejmech.2015.06.006
  9. Barrett I, Meegan MJ, Hughes RB, et al. Synthesis, biological evaluation, structural-activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators. Bioorg Med Chem 2008 Nov 1;16(21):9554-9573. doi:10.1016/j.bmc.2008.09.035
  10. Yenigun VB, Ozpolat B, Kose GT. Response of CD44+/CD24-/low breast cancer stem/progenitor cells to tamoxifen‑ and doxorubicin‑induced autophagy. Int J Mol Med 2013 Jun;31(6):1477-1483. doi: 10.3892/ijmm.2013.1342
  11. Kharbanda A, Rajabi H, Jin C, Raina D, Kufe D. Oncogenic MUC1-C promotes tamoxifen resistance in human breast cancer. Mol Cancer Res. 2013 Jul;11(7):714-723. doi: 10.1158/1541-7786.MC