RESUMEN
BACKGROUND: Inflammation is a key element in tumor progression, over time, persistent inflammation causes damage to DNA and leads to cancer. The relationship between chronic inflammation and tumor development is well established, blocking of which can help in cancer prevention and treatment in the future. OBJECTIVE: Hence, with this background, the present study aims to evaluate the anti-inflammatory and anticancer potential of Cassia auriculata (CA) solvent fractions through in silico and in vitro means, respectively. METHODS: Generally, inflammatory mediators play a key task in chronic inflammation, following its inflection was chosen for their interactions with nine structurally varied phytoconstituents of CA identified through GCMS. The ethanolic extract of CA was assessed for its apoptotic effects on A549 lung cancer cells by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, JC-10 staining, DNA fragmentation assay and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: The interactions between bioactive components and target protein revealed that important molecules like 5,7-dihydroxy-2-[2-nethoxyphenyl]- 4H-1-Benzopyran-4-one, a flavonoid, and three other components can bind target interleukin 1-beta associated with lung cancer. In vitro data also confirmed that the diverse active components of CA extract might follow the intrinsic mitochondrial pathway to provoke cancer cell death. CONCLUSION: Hence, these findings strongly propose that Cassia auriculata (CA) solvent fractions could be exploited in the future to design ligands for obtaining novel leads for treating chronic inflammation linked with lung cancer, and also the extracts of CA can be recommended as a potential agent for lung cancer chemotherapy.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Cassia/química , Flavonoides/farmacología , Inflamación/tratamiento farmacológico , Interleucina-1beta/antagonistas & inhibidores , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Células A549 , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Flavonoides/aislamiento & purificación , Humanos , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The present study is an attempt to evaluate the in vitro anti-inflammatory and in silico anticancer potentials of the plant Cassia auriculata (CA). The aerial parts of CA were subjected to solvent extraction, and the extracts were fractionised by gas chromatography and mass spectrometry analysis for its phytochemical content. The antiinflammatory activity of the extracts were confirmed by the IC50 value of 125.02â µg/ml for red blood cell membrane stabilisation and 195.7â µg/ml for inhibition of protein denaturation activity. The interaction of bioactive compounds of CA ethanol extract with target protein was predicted through molecular docking studies, serine/threonine-protein kinase B (AKT1), responsible for development and progression of lung cancer using AutoDock tools. Extensive studies have been carried out on a range of kinase inhibitors targeting Akt, but obtaining promising results is a challenge yet due to its toxicity and resistance issues. Yohimbine, undecanoic acid 10-methyl-ethyl ester and chrysin significantly bind to the target protein with least binding energy. Hence, the present paper establishes the anti-inflammatory and anticancer capacities of CA ethanol extract as an alternative to the existing therapeutic approach to inflammation and cancer through a systematic in vitro and in silico approaches supplementing the findings.