ABSTRACT
Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC50 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC50 476.0 µg/mL) and HepG2 (CC50 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.
ABSTRACT
Species of the genus Lippia are rich in essential oils and have shown antibacterial properties, which may be related to oils' chemical composition. The present work aimed to evaluate the antimicrobial potential of Lippia origanoides Kunth against two bacteria strains: Escherichia coli and Staphylococcus aureus. Leaf essential oils were obtained by hydrodistillation in a modified Clevenger-type apparatus, and their chemical composition was determined by gas chromatography coupled to mass spectrometry (GC/MS) and flame ionization detection (GC/FID). We identified 28 compounds, representing 98.87% of the total concentration of the essential oil. The compounds identified at the highest concentrations were 1,8-cineole (35.04%), carvacrol (11.32%), p-cymene (8.53%), α-pinene (7.17%), and γ-terpinene (7.16%). The leaf essential oil of L. origanoides showed antibacterial action on biological isolates of Escherichia coli and Staphylococcus aureus. For Escherichia coli, the oil presented bactericidal action at concentrations of 5-20 µL/mL. Regarding Staphylococcus aureus, the bactericidal effect was noted at 20 µL/mL and the bacteriostatic action was noted around 2.5-10 µL/mL. Given the results obtained, L. origanoides essential oil showed promising biological potential against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, thus encouraging further studies on substances isolated from this species to contribute to the development of new antimicrobial drugs.
