Bladder cancer has a high incidence and mortality rate worldwide. Existing treatment methods often face the challenges, such as drug resistance, recurrence and metastasis. These challenges drive our effect to explore new therapeutic compounds. 19-Hydroxycytochalasin B (19-HCB) is a new cytochalasin isolated from marine fungus. Previous studies have confirmed that its structural analogues have good anti-tumor activity, but the anti-tumor activity and mechanism of 19-HCB remain unclear. This study aims to evaluate the in vitro anti-tumor activity of 19-HCB and explore the mechanism of its action in human bladder cancer J82 cells. The anti-tumor activity was comprehensively evaluated through analyzing cell growth by MTT assay, cell scratch assay, high-content imaging and flow cytometry, colony formation and other experiments. The results showed that 19-HCB exhibited the strongest proliferative inhibitory activity (IC50 = 0.59 μmol·L-1) against bladder cancer J82 cells and could significantly inhibit the migration of J82 cells. Its mechanism of action is closely related to inducing apoptosis, manifested as the upregulation of pro-apoptotic proteins BIM and BAX and the down-regulation of anti-apoptotic protein survivin. Meanwhile, the expression of cell cycle regulatory protein p21 is upregulated while that of CDK1 is downregulated. Additionally, 19-HCB can also inhibit the AKT signaling pathway. In summary, 19-HCB exerts anti-bladder cancer effects by inducing apoptosis, inhibiting migration and regulating multiple key signaling pathways, and is a candidate drug lead compound with development potential.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |