Article
Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening
Oncotarget
(2015)
Abstract
The limited translational value in clinic of analyses performed on 2-D cell cultures has prompted a shift toward the generation of 3-dimensional (3-D) multicellular systems. Here we present a spontaneously-forming in vitro cancer spheroid model, referred to as spheroidsMARY-X, that precisely reflects the pathophysiological features commonly found in tumor tissues and the lymphovascular embolus. In addition, we have developed a rapid, inexpensive means to evaluate response following drug treatment where spheroid dissolution indices from brightfield image analyses are used to construct dose-response curves resulting in relevant IC50 values. Using the spheroidsMARY-X model, we demonstrate the unique ability of a new class of molecules, containing the caged Garcinia xanthone (CGX) motif, to induce spheroidal dissolution and apoptosis at IC50 values of 0.42 +/−0.02 μM for gambogic acid and 0.66 +/−0.02 μM for MAD28. On the other hand, treatment of spheroidsMARY-X with various currently approved chemotherapeutics of solid and blood-borne cancer types failed to induce any response as indicated by high dissolution indices and subsequent poor IC50 values, such as 7.8 +/−3.1 μM for paclitaxel. Our studies highlight the significance of the spheroidsMARY-X model in drug screening and underscore the potential of the CGX motif as a promising anticancer pharmacophore.
Disciplines
Publication Date
August 28, 2015
DOI
http://dx.doi.org/10.18632/oncotarget.4013
Citation Information
M. A. Theodoraki, C. I. Rezende, O. Chantarasriwong, A. D. Corben, et al.. "Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening" Oncotarget Vol. 6 Iss. 25 (2015) p. 21255 - 21267 Available at: http://works.bepress.com/mary-alpaugh/2/
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