A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer.
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| 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 (KRas(G12D); Trp53(R172H); 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.
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| Authors | 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 |
| Journal | Science translational medicine (Sci Transl Med) Vol. 4 Issue 156 Pg. 156ra139 (Oct 17 2012) ISSN: 1946-6242 [Electronic] United States |
| PMID | 23076356 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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