The Newly Synthetized Chalcone L1 Is Involved in the Cell Growth Inhibition, Induction of Apoptosis and Suppression of Epithelial-to-Mesenchymal Transition of HeLa Cells.
Tomas KurucMartin KelloKlaudia PetrovaZuzana KudlickovaPeter KubatkaJan MojzisPublished in: Molecules (Basel, Switzerland) (2021)
Over the past decades, natural products have emerged as promising agents with multiple biological activities. Many studies suggest the antioxidant, antiangiogenic, antiproliferative and anticancer effects of chalcones and their derivatives. Based on these findings, we decided to evaluate the effects of the newly synthetized chalcone L1 in a human cervical carcinoma cell (HeLa) model. Presented results were obtained by western blot and flow cytometric analyses, live cell imaging and antimigratory potential of L1 in HeLa cells was demonstrated by scratch assay. In the present study, we proved the role of L1 as an effective agent with antiproliferative activity supported by G2/M cell cycle arrest and apoptosis. Moreover, we proved that L1 is involved in modulating Transforming Growth Factor-β1 (TGF-β) signal transduction through Smad proteins and it also modulates other signalling pathways including Akt, JNK, p38 MAPK, and Erk1/2. The involvement of L1 in epithelial-to-mesenchymal transition was demonstrated by the regulation of N-cadherin, E-cadherin, and MMP-9 levels. Here, we also evaluated the effect of conditioned medium from BJ-5ta human foreskin fibroblasts in HeLa cell cultures with subsequent L1 treatment. Taken together, these data suggest the potential role of newly synthesized chalcone L1 as an anticancer-tumour microenvironment modulating agent.
Keyphrases
- cell cycle arrest
- pi k akt
- signaling pathway
- transforming growth factor
- cell death
- epithelial mesenchymal transition
- induced apoptosis
- endothelial cells
- cell proliferation
- single cell
- cell therapy
- induced pluripotent stem cells
- oxidative stress
- high resolution
- stem cells
- south africa
- human health
- pluripotent stem cells
- risk assessment
- combination therapy
- smoking cessation
- fluorescence imaging