Hinokinin, a lignan from Piper cubeba fruits induces apoptosis via reactive oxygen species-mediated mitochondrial dysfunction in MCF-7 breast cancer cells.

The phytochemical investigation of fruits of P. cubeba led to the isolation of sixteen compounds (1-16), including two 8 and 10 for the first time. The structures were established using spectroscopic analysis, including (1H, 13C, 2D NMR data and MS analysis). The crude extract, fractions and isolated compounds were tested for cytotoxicity against four human cancer cell lines, Viz. MDA-MB-231, MCF-7, HCT-116 and Mia-PaCa-2. Chloroform fraction exhibited significant cytotoxicity against MCF-7 cancer cell line, whereas compounds (2), hinokinin, and (6) 9S-O-methyl cubebin showed maximum cytotoxicity of 50-40% inhibition at 10 µM concentration against MCF-7, MDA-MB231, and Mia-PaCa-2. Hinokinin (2) didn't show any toxicity up to 100 μM concentration. The mechanistic assays revealed its role in inducing apoptosis in MCF-7 cells via ROS generation and MMP disruption. These results highlight P. cubeba as a source for anticancer compounds, warranting further research into the therapeutic applications of these bioactive substances in cancer treatment.