Journal article
Minnelide effectively eliminates CD133(+) side population in pancreatic cancer
Molecular cancer, Vol.14(1), pp.200-200
11/23/2015
DOI: 10.1186/s12943-015-0470-6
PMID: 26597727
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease hallmarked by limited patient survival. Resistance to chemotherapy, a major cause of treatment failure in PDAC patients, is often attributed to Cancer Stem Cells (CSCs). Pancreatic CSCs are a small subset of quiescent cells within a tumor represented by surface markers like CD133. These cells are responsible not only for tumor recurrence, but also poor prognosis based on their "stem-like" characteristics. At present, conventional therapy is directed towards rapidly dividing PDAC cells and thus fails to target the CSC population.
MIA PaCa-2, S2-013 and AsPC-1 were treated with 12.5 nM triptolide (12 T cells) for 7 days. The surviving cells were recovered briefly in drug-free growth media and then transferred to Cancer Stem cell Media (CSM). As a control, untreated cells were also transferred to CSM media (CSM). The 12 T and CSM cells were tested for stemness properties using RNA and protein markers. Low numbers of CSM and 12 T cells were implanted subcutaneously in athymic nude mice to study their tumorigenic potential. 12 T and CSM cells were sorted for CD133 expression and assayed for their colony forming ability and sphere forming ability. Invasiveness of 12 T cells, CSM and MIA PaCa-2 were compared using Boyden chamber assays.
Treated 12 T cells displayed increased expression of the surface marker CD133 and the drug transporter ABCG2 compared to untreated cells (CSM cells). Both 12 T and CSM cells formed subcutaneous tumors in mice confirming their tumor-initiating properties. When tested for invasion, 12 T cells had increased invasiveness compared to CSM cells. CD133(+) cells in both CSM and 12 T showed greater colony and sphere forming ability compared to CD133(-) cells from each group. Consistent with these data, when injected subcutaneously in mice, CD133(-) cells from CSM or 12 T did not form any tumors whereas CD133(+) cells from both groups showed tumor formation at a very low cell number. Despite pre-exposure to triptolide in 12 T CD133(+) cells, treatment of tumors formed by these cells with Minnelide, a triptolide pro-drug, showed significant tumor regression.
Our results indicated that triptolide enhanced and enriched the "stemness" in the PDAC cell lines at a low dose of 12.5 nM, but also resulted in the regression of tumors derived from these cells.
Details
- Title: Subtitle
- Minnelide effectively eliminates CD133(+) side population in pancreatic cancer
- Creators
- Alice Nomura - University of MinnesotaOlivia McGinn - University of MinnesotaVikas Dudeja - University of MinnesotaVeena Sangwan - University of MinnesotaAshok K Saluja - University of MinnesotaSulagna Banerjee - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Molecular cancer, Vol.14(1), pp.200-200
- DOI
- 10.1186/s12943-015-0470-6
- PMID
- 26597727
- NLM abbreviation
- Mol Cancer
- ISSN
- 1476-4598
- eISSN
- 1476-4598
- Grant note
- T32 DA007097-32 / NIDA NIH HHS R01 CA184274 / NCI NIH HHS R01 CA170946 / NCI NIH HHS R01-CA184274 / NCI NIH HHS R01-CA170946 / NCI NIH HHS R01 CA124723 / NCI NIH HHS T32 DA007097 / NIDA NIH HHS
- Language
- English
- Date published
- 11/23/2015
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244574602771
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