Endoplasmic Reticulum Stress-Induced Apoptotic Effects of Novel 1-Pyrroline (3,4-Dihydro-2H-pyrrole) Derivatives on Breast Cancer Cells

Atmaca H., Ilhan S., Korkmaz E., Zora M.

Chemistry and Biodiversity, cilt.19, sa.7, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 7
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/cbdv.202200123
  • Dergi Adı: Chemistry and Biodiversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: 1-pyrroline, apoptosis, ER stress, breast cancer
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Heterocyclic compounds have emerged as promising and appealing scaffolds for developing effective antitumor agents. Here, the effects of synthesized 24 different 1-pyrroline derivatives (PDs) containing substituted aryl sulfide moiety were investigated on human breast cancer cell lines. The viability of cells was assessed via MTT assay. Reactive oxygen species (ROS) generation was analyzed via fluorescent dye CM-H2DCFDA. Apoptotic cells were determined via flow cytometry. Endoplasmic reticulum (ER) stress-associated protein levels were analyzed via western blot analysis. Four of the PDs (PD-12, -14, -16 and -17) had great cytotoxic selectivity against breast cancer cells. Apoptotic cell death was induced by PDs via the generation of ROS. PDs significantly increased the GRP78, p-PEAK, p-eIF2α, and CHOP protein levels indicating ER stress in breast cancer cells. These results imply that newly synthesized PDs may be potential anticancer agents as they selectively inhibit breast cancer cells.