Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

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 frondoside...

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Bibliographic Details
Published in:Marine Drugs
Main Authors: Al Shemaili, Jasem, Parekh, Khatija A., Newman, Robert A., Hellman, Björn, Woodward, Carl, Adem, Abdu, Collin, Peter, Adrian, Thomas E.
Format: Article in Journal/Newspaper
Language:English
Published: Uppsala universitet, Institutionen för farmaceutisk biovetenskap 2016
Subjects:
frondoside A
pancreatic cancer
cancer
pharmacokinetics
Pharmacology and Toxicology
Farmakologi och toxikologi
Cucumaria frondosa
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-299910
https://doi.org/10.3390/md14060115
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Summary: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.

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