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Network pharmacology and in vitro experiments reveal sophoridine-induced apoptosis and G1 phase arrest via
Abstract:
Bladder cancer (BLCA), a common primary malignancy, exhibits resistance to conventional chemotherapeutic agents. Sophoridine (SR) is a quinoline alkaloid derived from the traditional Chinese herb Sophora alopecuroides L., which belongs to the legume family Sophoraceae. SR is reported to exert growth-inhibitory effects against several cancers. However, the mechanisms underlying the growth-inhibitory effects of SR on BLCA have not been elucidated. This study performed molecular and cellular experiments to verify the growth-inhibitory effects of SR on BLCA and the underlying mechanisms. SR inhibited cell proliferation and promoted apoptosis and G1-phase arrest through the PI3K/AKT/FoxO3a signaling pathway. More interestingly, the effects of SR can be attributed to the accumulation of reactive oxygen species (ROS) in vivo. ROS may be the upstream factor of this pathway. Additionally, SR inhibited the migration and invasion of BLCA cells in a concentration-dependent or time-dependent manner. This is the first study to demonstrate the ROS-dependent PI3K/AKT/FoxO3a pathway-mediated anticancer effect of SR and the anticancer mechanism of SR in BLCA. The correlation between SR-induced ROS-dependent cell proliferation inhibition, apoptosis, cell cycle arrest, and PI3K/AKT/FoxO3a suggests that SR is a promising novel therapeutic for BLCA.
Insights
Sophoridine (SR) inhibits bladder cancer (BLCA) growth by promoting apoptosis and cell cycle arrest. This effect is mediated by reactive oxygen species (ROS) and the PI3K/AKT/FoxO3a pathway, suggesting SR as a potential BLCA therapy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Bladder cancer (BLCA) is a common malignancy often resistant to chemotherapy.
- Sophoridine (SR), a quinoline alkaloid from Sophora alopecuroides L., shows anti-cancer potential but its mechanism in BLCA is unknown.
Purpose of the Study:
- To investigate the anti-cancer mechanisms of Sophoridine (SR) in bladder cancer (BLCA).
- To elucidate the role of reactive oxygen species (ROS) and the PI3K/AKT/FoxO3a pathway in SR's effects on BLCA.
Main Methods:
- Molecular and cellular experiments were conducted to assess SR's impact on BLCA cells.
- Analysis included cell proliferation, apoptosis, cell cycle progression, migration, and invasion assays.
- The involvement of the PI3K/AKT/FoxO3a pathway and ROS generation was investigated.
Main Results:
- SR significantly inhibited BLCA cell proliferation and promoted apoptosis.
- SR induced G1-phase arrest via the PI3K/AKT/FoxO3a signaling pathway.
- SR's anti-cancer effects were linked to increased reactive oxygen species (ROS) accumulation, which may act upstream of the pathway.
- SR also reduced BLCA cell migration and invasion in a dose- and time-dependent manner.
Conclusions:
- This study demonstrates the anti-cancer mechanisms of SR in BLCA, highlighting its ROS-dependent inhibition of proliferation, induction of apoptosis, and cell cycle arrest through the PI3K/AKT/FoxO3a pathway.
- SR shows promise as a novel therapeutic agent for bladder cancer.
