A preclinical evaluation of minnelide as a therapeutic agent against pancreatic cancer

Rohit Chugh, Veena Sangwan, Satish P. Patil, Vikas Dudeja, Rajinder K. Dawra, Sulagna Banerjee, Robert J. Schumacher, Bruce R. Blazar, Gunda I. Georg, Selwyn M. Vickers, Ashok K. Saluja

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

Pancreatic cancer is one of the most lethal human malignancies with an all-stage 5-year survival frequency of <5%, which highlights the urgent need for more effective therapeutic strategies. We have previously shown that triptolide, a diterpenoid, is effective against pancreatic cancer cells in vitro as well as in vivo. However, triptolide is poorly soluble in water, limiting its clinical use. We therefore synthesized a water-soluble analog of triptolide, named Minnelide. The efficacy of Minnelide was tested both in vitro and in multiple independent yet complementary in vivo models of pancreatic cancer: an orthotopic model of pancreatic cancer using human pancreatic cancer cell lines in athymic nude mice, a xenograft model where human pancreatic tumors were transplanted into severe combined immunodeficient mice, and a spontaneous pancreatic cancer mouse model (KRasG12D; Trp53R172H; Pdx-1Cre). In these multiple complementary models of pancreatic cancer, Minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival. Together, our results suggest that Minnelide shows promise as a potent chemotherapeutic agent against pancreatic cancer, and support the evaluation of Minnelide in clinical trials against this deadly disease.

Original languageEnglish (US)
Article number156ra139
JournalScience Translational Medicine
Volume4
Issue number156
DOIs
StatePublished - Oct 17 2012

ASJC Scopus subject areas

  • Medicine(all)

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