Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Human bladder cancer presents a significant global health challenge with limited therapeutic advancements.
• Novel therapeutic strategies are crucial to improve patient survival rates for bladder cancer.
• Actein (ACT), a triterpene glycoside from black cohosh, has demonstrated anti-cancer properties in breast cancer models.

Purpose of the Study:

• To investigate the anti-cancer effects of Actein (ACT) on human bladder cancer cells.
• To elucidate the molecular mechanisms underlying ACT's action in bladder cancer.
• To evaluate ACT's therapeutic potential and safety in vivo.

Main Methods:

• Cell proliferation assays and cell cycle analysis to assess ACT's impact on bladder cancer cell growth.
• Analysis of autophagy and apoptosis markers, including LC3B-II, Caspases, and PARP cleavage.
• Investigation of the roles of reactive oxygen species (ROS), JNK, AKT, and mTOR signaling pathways.

Main Results:

• ACT significantly inhibited bladder cancer cell proliferation by inducing G2/M cell cycle arrest.
• ACT triggered both autophagy and apoptosis, evidenced by autophagosome formation and increased cleavage of key apoptotic proteins.
• ACT reduced ROS and p-JNK levels, while de-phosphorylating AKT and mTOR, suggesting these pathways mediate its effects.

Conclusions:

• Actein (ACT) suppresses bladder cancer cell proliferation and induces cell death via autophagy and apoptosis.
• The anti-cancer effects of ACT involve modulation of ROS/JNK activation and inhibition of the AKT/mTOR pathway.
• ACT demonstrates potential as an effective and safe therapeutic candidate for human bladder cancer.