Synergy of Pancratistatin and Tamoxifen on breast cancer cells in inducing apoptosis by targeting mitochondria.

Pancratistatin (PST), a natural compound obtained from the Hawaiian spider lily, is known to be specific and selective in inducing apoptosis in multiple cancer cell lines while sparing noncancerous cells and cell lines. Here we report the ability of PST to induce apoptosis specifically in human breast cancer cell lines MCF-7 and Hs-578-T compared to their non cancerous counterparts. In cancer cells PST caused increased levels of reactive oxygen species (ROS), decreased ATP and mitochondrial membrane permeabilization indicating the activation of the mitochondrial pathway of apoptosis. In combination with the anti-estrogen Tamoxifen, PST had a synergic effect. Both compounds caused increased production of ROS when applied to isolated mitochondria from these cancer cell lines supporting the observation that Tamoxifen might work through mechanisms distinct from the canonical estrogen receptor antagonism.