چکیده (انگلیسی):

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.