Zn(II) 5,5-Diethylbarbiturate Complex Selectively Induces Apoptosis in Breast Cancer and Breast Cancer Stem-Like Cells


Tsochantaridis I., Pappa A., Dere E., Arı F.

CHEMISTRY & BIODIVERSITY, cilt.19, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/cbdv.202101001
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: breast cancer, breast cancer stem cells, apoptosis, Zn(II) complex, ENHANCED CYTOTOXIC ACTIVITY, RESISTANCE, METALS
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

The biological activities of Zn(II) compounds have been extensively studied in recent years. In this study, the growth suppressive effect of Zn(II) 5,5-diethylbarbiturate complex on MCF-7 and MDA-MB-231 human breast cancer cells was determined by SRB and ATP viability assays and apoptosis-inducing effect by double staining method. Significant increase in cytokeratin 18 level, caspase 3/7 activity and annexin-V upregulation prove that Zn(II) complex has apoptotic effect in breast cancer cells. Intrinsic apoptosis pathway in MCF-7 cells and extrinsic apoptosis pathway in MDA-MB-231 cells was determined by Western blot (PARP, Cleave PARP, BAX, COX4, RIP, Caspase 8, Split Caspase 8, DR4 and B-Actin) and RT-PCR (PARP, Fas, Bcl-2, TNF10A, P53) analysis. No reduction of viability was found in MCF-710A healthy breast cells treated with Zn(II) complex. In breast cancer stem-like cells (MCF-7s), the Zn(II) complex was found to have a cytotoxic effect and to activate the apoptotic pathway. As a result, it was concluded that Zn(II) complex has anti-proliferative and apoptotic effects on breast cancer and breast cancer stem-like cells. Also this complex prevents the metastatic effect of cancer cells and does not effect to healthy cells so this complex has a specific effect on cancer cells. These findings might shed light on the discovery of new chemotherapeutic agents.