Abstract
BackgroundGlobally, head and neck cancer is the sixth most common cancer. Despite the advancement in treatment, drug resistance remains a major cause for setback. In an earlier work, the authors reported that Boswellia dalzielii (Hutch) stem bark exhibited dose-dependent cytotoxicity in head and neck cancer cells, AW8507. Therefore, the cell death induction effect of Boswellia dalzielii stem bark chloroform extract in head and neck cancer cell line, AW8507, and its derived constituent on cell cycle and apoptosis proteins was further investigated.MethodsThe cell death induction activity of the Boswellia dalzielii stem bark chloroform fraction (CLBD) in AW8507 was determined using Annexin V-FITC/PI staining in flow cytometry. High-performance liquid chromatography-mass spectrometry was employed for compounds analysis of the CLBD, and reverse virtual screening was used to identify the mechanism of action of the compound, acetyl-11-keto-beta-boswellic acid, that was elucidated in the Boswellia dalzielii chloroform fraction.ResultsThe data obtained showed that Boswellia dalzielii stem bark Chloroform extract increased the percentage of cells presenting for early apoptosis from 4.14 to 10.10% in AW8507 cells. High-performance liquid chromatography-mass spectrometry analysis of the chloroform fraction identified acetyl-11-keto-beta-boswellic acid. Reverse virtual screening on selected proteins showed that acetyl-11-keto-beta-boswellic acid is a multi-protein target compound. It binds preferably to phosphorylated-cyclin dependent kinase 1 (p-CDK1) (binding score = − 9.2 kcal/mol), blocking the activation of cyclin B-CDK1 needed for cell cycle progression at G2/M phase of the cell cycle. Acetyl-11-keto-beta-boswellic acid also binds more tightly with αβ tubulin (binding score = 8.9 kcal/mol) than with the standard drug, docetaxel (binding score = 8.3 kcal/mol).ConclusionsThe results obtained confirmed the culpability of Boswellia dalzielii-derived acetyl-11-keto-beta-boswellic acid in the obstruction of the cell cycle progression in head and neck cancer cell line, AW8507; and the induction of apoptosis earlier reported for Boswellia dalzielii (Hutch) stem bark. Additional in vitro and/or in vivo studies would be required to validate in silico observations.
Highlights
Head and neck cancer is the sixth most common cancer
Boswellia dalzielii stem bark induced apoptosis in head and neck squamous cell carcinoma (HNSCC) As shown in Fig. 3, there was an increase in the percentage of cells presenting for early apoptosis (Q4), from 4.14 to 10.10%, and a significant reduction in the percentage of viable cells from 94.20% in the untreated control cells to 86.42% observed in the chloroform fraction of Boswellia dalzielii stem bark (CLBD) treated cells (Q1)
HPLC–MS analysis of Boswellia dalzielii stem bark chloroform fraction revealed the presence of acetyl‐11‐keto‐beta‐boswellic acid (AKBA) The HPLC–MS analysis of chloroform extract exhibited several compounds within the total ion chromatogram (TIC) (m/z 50–1000)
Summary
Head and neck cancer is the sixth most common cancer. Despite the advancement in treatment, drug resistance remains a major cause for setback. The authors reported that Boswellia dalzielii (Hutch) stem bark exhibited dose-dependent cytotoxicity in head and neck cancer cells, AW8507. The cell death induction effect of Boswellia dalzielii stem bark chloroform extract in head and neck cancer cell line, AW8507, and its derived constituent on cell cycle and apoptosis proteins was further investigated. The cytotoxic activity of Boswellia dalzielii gum resin and leaves were previously investigated on brine shrimp and ovarian cancer cells, respectively [9, 10]. The authors reported that Boswellia dalzielii stem bark exhibited dose-dependent cytotoxic activity in head and neck squamous cell carcinoma (AW8507 cell line) and blocked the cell cycle progression at G2/M [11]. The aim of this study was to evaluate the cell death induction activity of the chloroform extract in AW8507 cells, determine the active constituent and its activity against selected enzymes in silico
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