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Mar. Drugs 2016, 14(6), 115;

Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

Department of Physiology, Faculty of Medicine, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE
Phoenix Biotechnology Inc., San Antonio, TX 78217, USA
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 75105, Sweden
Coastside Bio Resources, Deer Isle, ME 04627, USA
Department of Pharmacology, Faculty of Medicine, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE
Author to whom correspondence should be addressed.
Academic Editors: Keith B. Glaser and Peer B. Jacobson
Received: 14 April 2016 / Revised: 15 May 2016 / Accepted: 6 June 2016 / Published: 17 June 2016
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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 ~1 µM. Frondoside B was less potent (EC50 ~2.5 µM). Frondoside C and the aglycone had no effect. At 100 µg/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cpmax was 129 nM, Cltb was 6.35 mL/min/m2, and half-life was 510 min. With i.p. administration the Cpmax was 18.3 nM, Cltb was 127 mL/min/m2 and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 µg/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. View Full-Text
Keywords: frondoside A; pancreatic cancer; cancer; pharmacokinetics frondoside A; pancreatic cancer; cancer; pharmacokinetics

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Al Shemaili, J.; Parekh, K.A.; Newman, R.A.; Hellman, B.; Woodward, C.; Adem, A.; Collin, P.; Adrian, T.E. Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer. Mar. Drugs 2016, 14, 115.

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