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Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2014 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 7, 1391-1398 p.Article in journal (Refereed) Published
Abstract [en]

Pancreatic cancer has a very poor prognosis. While gemcitabine is the mainstay of therapy and improves quality of life, it has little impact on survival. More effective treatments are desperately needed for this disease. Frondoside A is a triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A potently inhibits pancreatic cancer cell growth and induces apoptosis in vitro and in vivo. The aim of the present study was to investigate whether frondoside A could enhance the anti-cancer effects of gemcitabine. Effects of frondoside A and gemcitabine alone and in combination on proliferation were investigated in two human pancreatic cancer cell lines, AsPC-1 and S2013. To investigate possible synergistic effects, combinations of low concentrations of the two drugs were used for a 72 h treatment period in vitro. Growth inhibition was significantly greater with the drug combinations than their additive effects. Combinations of frondoside A and gemcitabine were tested in vivo using the athymic mouse model. Xenografts of AsPC-1 and S2013 cells were allowed to form tumours prior to treatment with the drugs alone or in combination for 30 days. Tumours grew rapidly in placebo-treated animals. Tumour growth was significantly reduced in all treatment groups. At the lowest dose tested, gemcitabine (4 mg/kg/dose), combined with frondoside A (100 mu g/kg/day) was significantly more effective than with either drug alone. To conclude: The present data suggest that combinations of frondoside A and gemcitabine may provide clinical benefit for patients with pancreatic cancer.

Place, publisher, year, edition, pages
2014. Vol. 50, no 7, 1391-1398 p.
Keyword [en]
Pancreatic cancer, Frondoside A, Gemcitabine
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-224321DOI: 10.1016/j.ejca.2014.01.002ISI: 000333805500019OAI: oai:DiVA.org:uu-224321DiVA: diva2:718009
Available from: 2014-05-19 Created: 2014-05-09 Last updated: 2014-05-19Bibliographically approved

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Al Shemaili, JasemHellman, BjörnNyberg, Fred
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