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Cytotoxicity and molecular docking analysis of racemolactone I, a new sesquiterpene lactone isolated from Inula racemosa
CONTEXT: Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds. OBJECTIVE: To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots. MATERIALS...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274518/ https://www.ncbi.nlm.nih.gov/pubmed/35294328 http://dx.doi.org/10.1080/13880209.2021.1946090 |
Sumario: | CONTEXT: Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds. OBJECTIVE: To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots. MATERIALS AND METHODS: The column chromatography of I. racemosa ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action. RESULTS: The isolated compound was identified as racemolactone I (compound 1). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound 1 (IC(50) = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. In silico studies exhibited that compound 1 binds to the active site of Polo-like kinase-1 and forms a stable complex. CONCLUSIONS: Racemolactone I was identified as potential anticancer agent, which can further be confirmed by in vivo investigations. |
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