PMID- 34165807 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20220125 IS - 1521-4184 (Electronic) IS - 0365-6233 (Linking) VI - 354 IP - 10 DP - 2021 Oct TI - 4-Propargyl-substituted 1H-pyrroles induce apoptosis and autophagy via extracellular signal-regulated signaling pathway in breast cancer. PG - e2100170 LID - 10.1002/ardp.202100170 [doi] AB - Novel pyrrole derivatives (PDs) with propargyl units (1-7) were investigated for their anticancer activity on breast cancer cells. The MTT assay was used to assess the cell viability. Morphological changes in human breast cancer cells were visualized under a phase-contrast microscope. Apoptosis and autophagy were detected using the DNA fragmentation assay and staining by autophagic vacuoles, respectively. The levels of apoptosis- and autophagy-related proteins such as cytochrome c, Bcl-2, LC3-I/II were investigated by Western blot analysis. The effect of PDs on the ERK1/2 signaling pathway was investigated using specific inhibitors. All the tested PDs were found to be active in the range of 36.7 +/- 0.2 to 459.7 +/- 4.2 microM. Compounds 3 and 4 showed cytotoxic activity in breast cancer cells, but were found to be safer with lower cytotoxicity on human nontumorigenic epithelial breast cells. Compound 4 induced apoptosis, whereas compound 3 induced autophagy. Both compounds inhibited the ERK signaling pathway in breast cancer cells. The present study revealed that both synthesized PDs induced different programmed cell death types by inhibiting the ERK signaling pathway in two genotypically different breast cancer cells. Therefore, novel PDs might be promising anticancer agents for breast cancer therapy and further structural modifications of PDs may yield promising anticancer agents. CI - (c) 2021 Deutsche Pharmazeutische Gesellschaft. FAU - Atmaca, Harika AU - Atmaca H AUID- ORCID: 0000-0002-8459-4373 AD - Department of Biology, Faculty of Science and Letters, Manisa Celal Bayar University, Manisa, Turkey. FAU - Ilhan, Suleyman AU - Ilhan S AD - Department of Biology, Faculty of Science and Letters, Manisa Celal Bayar University, Manisa, Turkey. FAU - Yilmaz, Elif Serel AU - Yilmaz ES AD - Department of Chemistry, Middle East Technical University, Ankara, Turkey. FAU - Zora, Metin AU - Zora M AUID- ORCID: 0000-0001-7764-2288 AD - Department of Chemistry, Middle East Technical University, Ankara, Turkey. LA - eng PT - Journal Article DEP - 20210624 PL - Germany TA - Arch Pharm (Weinheim) JT - Archiv der Pharmazie JID - 0330167 RN - 0 (Antineoplastic Agents) RN - 0 (Pyrroles) SB - IM MH - Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology MH - Apoptosis/*drug effects MH - Autophagy/drug effects MH - Breast Neoplasms/*drug therapy/pathology MH - Cell Line MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Epithelial Cells/drug effects MH - Female MH - Humans MH - MAP Kinase Signaling System/drug effects MH - Pyrroles/chemical synthesis/chemistry/*pharmacology MH - Signal Transduction/drug effects MH - Structure-Activity Relationship OTO - NOTNLM OT - ERK1/2 OT - apoptosis OT - autophagy OT - cytotoxicity OT - pyrrole derivatives EDAT- 2021/06/25 06:00 MHDA- 2022/01/27 06:00 CRDT- 2021/06/24 12:36 PHST- 2021/06/06 00:00 [revised] PHST- 2021/05/05 00:00 [received] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/06/25 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/06/24 12:36 [entrez] AID - 10.1002/ardp.202100170 [doi] PST - ppublish SO - Arch Pharm (Weinheim). 2021 Oct;354(10):e2100170. doi: 10.1002/ardp.202100170. Epub 2021 Jun 24.