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Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer
United Arab Emirates Univ, Fac Med, Dept Physiol, POB 17666, Al Ain, U Arab Emirates..
United Arab Emirates Univ, Fac Med, Dept Physiol, POB 17666, Al Ain, U Arab Emirates..
Phoenix Biotechnol Inc, San Antonio, TX 78217 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2016 (English)In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 14, no 6, 115Article in journal (Refereed) PublishedText
Abstract [en]

The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of similar to 1 mu M. Frondoside B was less potent (EC50 similar to 2.5 mu M). Frondoside C and the aglycone had no effect. At 100 mu g/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cp-max was 129 nM, Cl-tb was 6.35 mL/min/m(2), and half-life was 510 min. With i.p. administration the Cp-max was 18.3 nM, Cl-tb was 127 mL/min/m(2) and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 mu g/kg/day i.p.) markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer.

Place, publisher, year, edition, pages
2016. Vol. 14, no 6, 115
Keyword [en]
frondoside A, pancreatic cancer, cancer, pharmacokinetics
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-299910DOI: 10.3390/md14060115ISI: 000378770300012OAI: diva2:950351
Available from: 2016-07-29 Created: 2016-07-29 Last updated: 2016-07-29Bibliographically approved

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