Abstract
The current study was designed to investigate the antioxidant and cytotoxic activities of Thonningia sanguinea whole-plant extract. The total phenolic content was determined using Folin–Ciocalteu reagent and found to be 980.1 mg/g, calculated as gallic acid equivalents. The antioxidant capacity was estimated for the crude extract and the phenolic portion of T. sanguinea, whereupon both revealed a dose-dependent scavenging rate of DPPH• with EC50 values of 36.33 and 11.14 µg/mL, respectively. Chemical profiling of the plant extract was achieved by LC-ESI-TOF-MS/MS analysis, where 17 compounds were assigned, including ten compounds detected in the negative mode and seven detected in the positive mode. The phenolic portion exhibited promising cytotoxic activity against MCF-7 and HepG2 cells, with IC50 values of 16.67 and 13.51 μg/mL, respectively. Phenolic extract treatment caused apoptosis in MCF-7 cells, with total apoptotic cell death 18.45-fold higher compared to untreated controls, arresting the cell cycle at G2/M by increasing the G2 population by 39.7%, compared to 19.35% for the control. The apoptotic investigation was further validated by the upregulation of proapoptotic genes of P53, Bax, and caspases-3,8 9, and the downregulation of Bcl-2 as the anti-apoptotic gene. Bcl-2 inhibition was also virtualized by good binding interactions through a molecular docking study. Taken together, phenolic extract exhibited promising cytotoxic activity in MCF-7 cells through apoptosis induction and antioxidant activation, so further fractionation studies are recommended for the phenolic extract for specifying the most active compound to be developed as a novel anti-cancer agent.
Highlights
Cancer is a significant cause of death around the world [1,2]
T. sanguinea crude extract revealed EC50 values of 36.33 ± 1.02 μg/mL, and the phenolic portion exhibited EC50 values of 11.14 ± 1.06 μg/mL compared with the EC50 (24.42 ± 0.87 μg/mL) that was shown by the positive control, Trolox
Using LC-ESI-TOF-MS/MS analysis, 17 hits were newly identified in the plant extract
Summary
Cancer is a significant cause of death around the world [1,2]. Because of their independence from normal regulatory signals, cancer cells develop into tumor tissues, which can move to other organs in a process known as metastasis, which is responsible for approximately 90% of cancer-related fatalities [3,4,5]. Among the investigated plants were T. sanguinea roots, where its activity was studied against three human cancer cell lines, DLD-1 (colon), MCF-7 (breast), and M14 (melanoma). The study revealed moderate IC50 values of 40 ± 1.0, 55 ±1.2, and 43.2 ± 2.0, respectively [32] These findings prompted us to investigate the whole plant in terms of chemical composition using LC-ESI-TOF-MS/MS analysis, the total phenolic contents, and the antioxidant activity of T. sanguinea. The plant extract was found to inhibit the proliferation of human hepatocellular carcinoma cells (HepG-2) through apoptosis induction. The current study was planned to screen the cytotoxic activity of crude and phenolic extract of T. sanguinea against another panel of cancer cell lines, and investigate the apoptosis induction in the tested cell line. The scope of this paper was extended for exploring the virtual mechanism of binding of the identified compounds through molecular docking towards the Bcl-2 protein
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