Preliminary evaluation of antiproliferative and apoptotic activities of novel indolin-2-one derivatives.
Gulseren TurhalBusra DemirkanIzel Nermin BaslilarNimet Sule YuncuSultan Nacak BaytasAsuman Demiroglu-ZergerogluPublished in: Drug development research (2024)
Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl-2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin-2-one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines.
Keyphrases
- cell cycle arrest
- pi k akt
- signaling pathway
- cell proliferation
- cell death
- induced apoptosis
- structure activity relationship
- oxidative stress
- cell cycle
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- anti inflammatory
- dna damage
- optical coherence tomography
- computed tomography
- magnetic resonance imaging
- high glucose
- stem cells
- young adults
- high resolution
- stress induced
- single cell
- lymph node metastasis
- mesenchymal stem cells
- magnetic resonance