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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ftdoajarticles:oai:doaj.org/article:2dec5c87f9fa4351852110d254472133 2023-05-15T15:59:39+02:00 Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer Jasem Al Shemaili Khatija A. Parekh Robert A. Newman Björn Hellman Carl Woodward Abdu Adem Peter Collin Thomas E. Adrian 2016-06-01T00:00:00Z https://doi.org/10.3390/md14060115 https://doaj.org/article/2dec5c87f9fa4351852110d254472133 EN eng MDPI AG http://www.mdpi.com/1660-3397/14/6/115 https://doaj.org/toc/1660-3397 1660-3397 doi:10.3390/md14060115 https://doaj.org/article/2dec5c87f9fa4351852110d254472133 Marine Drugs, Vol 14, Iss 6, p 115 (2016) frondoside A pancreatic cancer cancer pharmacokinetics Biology (General) QH301-705.5 article 2016 ftdoajarticles https://doi.org/10.3390/md14060115 2022-12-30T23:37:24Z 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. Article in Journal/Newspaper Cucumaria frondosa Directory of Open Access Journals: DOAJ Articles Marine Drugs 14 6 115 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
frondoside A pancreatic cancer cancer pharmacokinetics Biology (General) QH301-705.5 |
spellingShingle |
frondoside A pancreatic cancer cancer pharmacokinetics Biology (General) QH301-705.5 Jasem Al Shemaili Khatija A. Parekh Robert A. Newman Björn Hellman Carl Woodward Abdu Adem Peter Collin Thomas E. Adrian Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
topic_facet |
frondoside A pancreatic cancer cancer pharmacokinetics Biology (General) QH301-705.5 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Jasem Al Shemaili Khatija A. Parekh Robert A. Newman Björn Hellman Carl Woodward Abdu Adem Peter Collin Thomas E. Adrian |
author_facet |
Jasem Al Shemaili Khatija A. Parekh Robert A. Newman Björn Hellman Carl Woodward Abdu Adem Peter Collin Thomas E. Adrian |
author_sort |
Jasem Al Shemaili |
title |
Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
title_short |
Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
title_full |
Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
title_fullStr |
Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
title_full_unstemmed |
Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer |
title_sort |
pharmacokinetics in mouse and comparative effects of frondosides in pancreatic cancer |
publisher |
MDPI AG |
publishDate |
2016 |
url |
https://doi.org/10.3390/md14060115 https://doaj.org/article/2dec5c87f9fa4351852110d254472133 |
genre |
Cucumaria frondosa |
genre_facet |
Cucumaria frondosa |
op_source |
Marine Drugs, Vol 14, Iss 6, p 115 (2016) |
op_relation |
http://www.mdpi.com/1660-3397/14/6/115 https://doaj.org/toc/1660-3397 1660-3397 doi:10.3390/md14060115 https://doaj.org/article/2dec5c87f9fa4351852110d254472133 |
op_doi |
https://doi.org/10.3390/md14060115 |
container_title |
Marine Drugs |
container_volume |
14 |
container_issue |
6 |
container_start_page |
115 |
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1766395572035518464 |