Scutebarbatine B Exerts Anti-Breast Cancer Activity by Inducing Cell Cycle Arrest and Apoptosis Through Multiple...

Area of Science:

• Pharmacology and Toxicology
• Oncology
• Natural Product Chemistry

Background:

• Breast cancer remains a leading cause of mortality in women, necessitating novel therapeutic strategies.
• Identifying effective anticancer compounds from natural sources is crucial for improving patient survival rates.
• Scutellaria barbata D. Don (S. barbata) is a traditional herb with potential medicinal properties.

Purpose of the Study:

• To investigate the anticancer effects of Scutebarbatine B (SBT-B), a diterpenoid alkaloid from S. barbata, on breast cancer.
• To elucidate the underlying molecular mechanisms responsible for SBT-B's anti-breast cancer activity in vitro and in vivo.

Main Methods:

• In vitro assays included cell viability, EdU, immunofluorescence, flow cytometry, TUNEL staining, Western blot, and ROS detection (DCFH-DA, DHE).
• In vivo efficacy was assessed using mice xenograft models.
• Key molecular pathways (pRB/E2F1, Akt/mTOR, IRE1/JNK) and apoptosis markers (caspase-8, -9, PARP) were analyzed.

Main Results:

• SBT-B suppressed breast cancer cell proliferation and induced G2/M phase arrest, downregulating cyclins and Cdc2.
• SBT-B triggered apoptosis by increasing caspase and PARP cleavage and elevated intracellular reactive oxygen species (ROS) generation.
• SBT-B inhibited tumor growth in vivo, suppressed pRB/E2F1 and Akt/mTOR pathways, and activated the IRE1/JNK pathway.

Conclusions:

• Scutebarbatine B (SBT-B) demonstrates significant anticancer activity against breast cancer by inducing DNA damage, cell cycle arrest, and apoptosis.
• ROS generation, inhibition of oncogenic signaling, and activation of the IRE1/JNK pathway are critical mechanisms underlying SBT-B's efficacy.
• SBT-B shows promise as a potential alternative therapeutic candidate for treating human breast cancer.