Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

Harsharan Dhillon, Shireen Chikara, Katie M. Reindl

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)309-318
Number of pages10
JournalToxicology Reports
Volume1
DOIs
StatePublished - Oct 1 2014

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Cell death
Pancreatic Neoplasms
DNA Damage
Reactive Oxygen Species
Cell Death
DNA
Tumors
Cell culture
Neoplasms
Animals
Growth
Cell Culture Techniques
Piper
Oxidative stress
piperlonguminine
Cell proliferation
Heterografts
Antioxidants
Cells
Oxidative Stress

Keywords

  • Natural products
  • Pancreatic cancer
  • ROS

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage. / Dhillon, Harsharan; Chikara, Shireen; Reindl, Katie M.

In: Toxicology Reports, Vol. 1, 01.10.2014, p. 309-318.

Research output: Contribution to journalArticle

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