Al Shemaili Jasem, Parekh Khatija A, Newman Robert A, Hellman Björn, Woodward Carl, Adem Abdu, Collin Peter, Adrian Thomas E
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.
Mar Drugs. 2016 Jun 17;14(6):115. doi: 10.3390/md14060115.
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.
海参皂苷是从大西洋海参（Cucumaria frondosa）中提取的三萜类糖苷。海参皂苷A可抑制多种癌症类型（包括胰腺癌）的生长、侵袭、转移和血管生成，并诱导细胞凋亡。我们比较了三种海参皂苷及其苷元的生长抑制作用，并将其与药代动力学和给药途径相关联。海参皂苷A能有效抑制胰腺癌细胞的生长，半数有效浓度（EC50）约为1 μM。海参皂苷B的效力较弱（EC50约为2.5 μM）。海参皂苷C和苷元没有作用。以100 μg/kg的剂量给CD₂F₁小鼠静脉推注海参皂苷A，血药峰浓度（Cpmax）为129 nM，清除率（Cltb）为6.35 mL/min/m²，半衰期为510分钟。腹腔注射时，Cpmax为18.3 nM，Cltb为127 mL/min/m²，半衰期为840分钟。口服给药无效。海参皂苷A（100 μg/kg/天，腹腔注射）显著抑制裸鼠体内癌异种移植物的生长。经口灌胃给予相同剂量则没有效果。未观察到海参皂苷A有急性毒性的证据。海参皂苷A是比其他海参皂苷更有效的癌症生长抑制剂。糖苷成分对生物活性至关重要。海参皂苷A只有全身给药时才有效。基于目前和之前的研究，海参皂苷A似乎是安全的，可能对癌症治疗有价值。
