Pancreatic cancer is one of the most deadly
cancers with a nearly 95% mortality rate. The poor response of
pancreatic cancer to currently available
therapies and the extremely low survival rate of
pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of
reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various
cancers. In this study, we investigated the potential of a known ROS inducer,
piperlongumine (PPLGM), a bioactive agent found in long peppers, to induce
pancreatic cancer cell death in cell culture and animal models. We found that PPLGM inhibited the growth of
pancreatic cancer cell cultures by elevating ROS levels and causing DNA damage. PPLGM-induced DNA damage and
pancreatic cancer cell death was reversed by treating the cells with an exogenous
antioxidant. Similar to the in vitro studies, PPLGM caused a reduction in
tumor growth in a xenograft mouse model of human
pancreatic cancer.
Tumors from the PPLGM-treated animals showed decreased Ki-67 and increased 8-OHdG expression, suggesting PPLGM inhibited
tumor cell proliferation and enhanced oxidative stress. Taken together, our results show that PPLGM is an effective inhibitor for in vitro and in vivo growth of
pancreatic cancer cells, and that it works through a ROS-mediated DNA damage pathway. These findings suggest that PPLGM has the potential to be used for treatment of
pancreatic cancer.