PMID- 32521878 OWN - NLM STAT- MEDLINE DCOM- 20210208 LR - 20210208 IS - 2241-6293 (Electronic) IS - 1107-0625 (Linking) VI - 25 IP - 2 DP - 2020 Mar-Apr TI - Antiproliferative effects of Norartocarpetin isoflavone in human lung carcinoma cells are mediated via targeting Ras/Raf/MAPK signalling pathway, mitochondrial mediated apoptosis, S-phase cell cycle arrest and suppression of cell migration and invasion. PG - 855-861 AB - PURPOSE: The main purpose of the current research work was to investigate the anticancer activity of norartocarpetin - a plant derived isoflavone -in human lung carcinoma cells NCI-H460 and normal lung cell line MRC-9 along with studying its effects on cellular apoptosis, DNA damage, cell migration and invasion and Ras/Raf/MAPK signalling pathways. METHODS: Cell proliferation was examined by CCK-8 assay while effects on apoptosis were evaluated by acridine orange (AO)/ethidium bormide (EB) staining and Comet assay using fluorescence microscopy. In vitro wound healing assay was used for checking the effects on cell migration and transwell assay for invasion while western blot was used to evaluate the effects on the expression of Ras/Raf/MAPK proteins. RESULTS: The results showed that Norartocarpetin led to dose-dependent cytotoxic effects in NCI-H460 cells showing an IC50 value of 22 muM while in normal lung cells, the cytotoxic effects were much lower as shown by higher IC50 value of 85 muM. It also led to dose-dependent apoptosis and induced DNA damage as shown by fluorescence microscopy. This molecule also inhibited cell migration and invasion dose-dependently, along with inhibiting MMP-9 expression. Norartocarpetin treatment also led to inhibition of the expression of Ras/Raf/MAPK proteins and also caused S-phase cell cycle arrest in these cells. CONCLUSION: Norartocarpetin has a significant anticancer activity in lung carcinoma cells and these effects are mediated via targeting apoptosis, DNA damage, cell migration and invasion, cell cycle and inhibiting Ras/Raf/MAPK signalling pathways. FAU - Guo, Ning AU - Guo N AD - Department of Cardio Thoracic Surgery, Puren Hospital of Wuhan University of Science and Technology, Wuhan 430081, China. FAU - Xiao, Yuanyang AU - Xiao Y FAU - Chen, Daxing AU - Chen D FAU - Wang, Jie AU - Wang J LA - eng PT - Journal Article PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (Isoflavones) SB - IM MH - Apoptosis MH - Cell Cycle Checkpoints/*drug effects MH - Cell Movement/*drug effects MH - Cell Proliferation MH - Flow Cytometry MH - Humans MH - Isoflavones/pharmacology/*therapeutic use MH - Lung Neoplasms/*drug therapy/pathology MH - MAP Kinase Signaling System/*drug effects MH - Neoplasm Invasiveness MH - Signal Transduction EDAT- 2020/06/12 06:00 MHDA- 2021/02/09 06:00 CRDT- 2020/06/12 06:00 PHST- 2020/06/12 06:00 [entrez] PHST- 2020/06/12 06:00 [pubmed] PHST- 2021/02/09 06:00 [medline] PST - ppublish SO - J BUON. 2020 Mar-Apr;25(2):855-861.