Data Availability StatementThe analyzed data sets generated during the study are available from the corresponding author on reasonable request. and promotion of cell apoptosis. It also indicated that germacrone functioned through modulations of cell cycle-associated protein expression and mitochondria-mediated apoptosis. Conclusion These findings will be valuable as the molecular basis for the germacrone-mediated anti-cancer effect against gastric cancer. are the principal bioactive constituents that have anti-inflammatory and anti-tumor properties [7, 8]. Germacrone is a natural bioactive compound found in essential oils [9, 10]. Studies on the biological activities of germacrone have demonstrated that it also possesses significant protective effects including anti-bacterial, anti-fungal, antifeedant, depressant, choleretic, antitussive and vasodilator activities [11C14]. These findings lead to the hypothesis in this study that germacrone might be involved in anti-tumor effect in human gastric cancer. Cell cycle arrest is an essential regulatory mechanism in cell proliferation and tumor development. A typical feature of cancer cells is the aperiodicity of cell cycle. DNA damage in the cells can activate the repairing system and many signal transduction pathways, which result in cell cycle arrest and apoptosis . G2/M phase is a major cell cycle checkpoint in cancer treatment because it allows the cells containing damaged DNA to repair the damage at the G2/M checkpoint . Germacrone has been reported to induce G0/G1 or G2/M phase cell cycle arrest in various cancer cell lines . Variations of cell cycle regulation in different types of cancer cells might due to differences associated with cell type . It is well studied that cyclin proteins play important roles in regulating cell cycle process . Cyclin B1, cell division cyclin 2 (cdc2) and cdc 25 are Acta2 crucial regulators associated with the G2 to M phase transition . Apoptosis is another core regulator of cell proliferation and cell death, Morusin which makes it a major factor that is targeted for cancer therapy. In the process of apoptosis, caspases function by executing cell death through different apoptotic stimuli [20, 21]. The distinct roles of caspase family members in cell apoptosis have been widely reported. Caspases associated with apoptosis have been classified based on their functions into the initiator, inhibitor and inflammatory caspases [22, 23]. The regulation of caspase activation involves in different cellular proteins including Bcl-2 protein family, which is known to be involved in the mitochondrial apoptosis pathway. They are classified into two groups as the pro-apoptotic (Bax, Bak) and anti-apoptotic (Bcl-2, Bcl-xl, Bcl-w, Mcl-1) proteins [24, 25]. Bax/Bcl-xl ratio is demonstrated to be highly associated with the extent of apoptosis . Here, the anti-cancer effect of germacrone and underlying mechanisms of its activity were investigated in human gastric Morusin cancer cell line BGC823. Changes of cell cycle arrest and apoptosis after germacrone treatment were assessed, and potential mechanisms were explored. Our findings will have valuable perception on the germacrone-mediated anti-cancer effect against gastric cancer. Methods Cell line and morphological assessment Human gastric cancer Morusin BGC823 cells (obtained from Cell Research Institute of the Chinese Academy of Science) were cultured in RPMI-1640 medium supplemented with 10% FBS, 100?g/mL penicillin and 100?g/mL streptomycin in a humidified incubator at 37?C with 5% CO2. Germacrone (Chengdu MUST Bio-technology CO., LTD, Chengdu, China) in serial concentrations as dissolved in DMSO (20, 40, 60, 80?M) were added to the culture medium. DMSO (0?M germacrone) was used as control. After incubation for 6, 12, 18, 24 and 48?h, cell morphological changes were monitored through an inverted microscope (Zeiss Axio Observer A1). Cell viability assessment using MTT assay BGC823 cells were seeded into 96-well plate (5??103) and were incubated for 24?h. Germacrone in serial concentrations as dissolved in DMSO (20, 40, 60, and 80?M) were added to the cells. DMSO (0?M germacrone) was used as control. After 12, 24, 48.
Data Availability StatementThe analyzed data sets generated during the study are available from the corresponding author on reasonable request