Mar. Drugs 2013, 11(9), 3258-3271; doi:10.3390/md11093258
Article

Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells

1 Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA 2 Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA 3 Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA
* Author to whom correspondence should be addressed.
Received: 5 July 2013; in revised form: 13 August 2013 / Accepted: 14 August 2013 / Published: 26 August 2013
(This article belongs to the Special Issue Marine Secondary Metabolites)
PDF Full-text Download PDF Full-Text [842 KB, uploaded 26 August 2013 14:52 CEST]
Abstract: Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC50 = 1.34 × 10−8 M). Analysis of dose response curves revealed pseudo-first order saturation kinetics, and the uncoupling of cytotoxicity from cell proliferation, thereby resulting in a widening of the therapeutic index. The formulation of PsA into HPβCD produced a 200-fold increase in potency over a DMSO formulation; we propose this could result from a constrained presentation of PsA to the receptor, which would limit non-specific binding. These results support the hypothesis that the non-specific receptor binding of PsA when formulated in DMSO has ostensibly masked prior estimates of specific activity, potency, and mechanism. Collectively, these results suggest that the formulation of PsA and compounds of similar chemical properties in HPβCD could result in significant pharmacological findings that may otherwise be obscured when using solvents such as DMSO.
Keywords: pseudopterosins; log P; human umbilical vein endothelial cells (HUVEC); proliferation; hydroxypropyl-beta-cyclodextrin (HPβCD)

Supplementary Files

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Day, D.R.; Jabaiah, S.; Jacobs, R.S.; Little, R.D. Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells. Mar. Drugs 2013, 11, 3258-3271.

AMA Style

Day DR, Jabaiah S, Jacobs RS, Little RD. Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells. Marine Drugs. 2013; 11(9):3258-3271.

Chicago/Turabian Style

Day, Daniel R.; Jabaiah, Suraya; Jacobs, Robert S.; Little, R. D. 2013. "Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells." Mar. Drugs 11, no. 9: 3258-3271.

Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert