Background:

Juglanin is a JNK activator.

Juglanin inhibits the proliferation of breast cancer cell in a dose- and time-dependent manner and presents less cytotoxic against the normal cells. Juglanin results in the accumulation of cancer cells in G2/M phase and a corresponding decrease in G0/G1 and S phases in both MCF-7 and SKBR3 cells. Juglanin up-regulates the expressions of phosphorylated Chk2, Chk2, phosphorylated Cdc25C, phosphorylated Cdc2, p27, cyclin D and down-regulates the levels of Cdc25C as well as Cdc2. The proportion of apoptosis is negligible for control cells, whereas 24 h of exposure of cells to Juglanin leads to a dose-dependent increase of apoptotic cells in both MCF-7 and SKBR3 cells. Juglanin significantly suppresses anti-apoptotic factor of Bcl-2 expression, and in contrast Bad and Bax are both up-regulated for Juglanin treatment. Juglanin markedly activates caspases and leads to Casapse-9, Casapse-8 and Caspase-3 cleavage. ROS generation is initiated by Juglanin and significantly increased by high concentrations of Juglanin. Juglanin also increases the level of JNK phosphorylation in both MCF-7 and SKBR3 cells[1].

Juglanin at doses of 5 and 10 mg/kg leads to significant decrease in tumor volume after 7 days of drug administration. 5 and 10 mg/kg Juglanin treatments do not cause weight loss in mice[1].

[1]. Sun ZL, et al. Juglanin induces apoptosis and autophagy in human breast cancer progression via ROS/JNK promotion. Biomed Pharmacother. 2017 Jan;85:303-312.