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Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening

  • Author(s): Theodoraki, MA
  • Rezende, CO
  • Chantarasriwong, O
  • Corben, AD
  • Theodorakis, EA
  • Alpaugh, ML
  • et al.
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 IC50values. Using the spheroidsMARY-Xmodel, 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 IC50values of 0.42 +/-0.02 μM for gambogic acid and 0.66 +/-0.02 μM for MAD28. On the other hand, treatment of spheroidsMARY-Xwith 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 IC50values, such as 7.8 +/-3.1 μM for paclitaxel. Our studies highlight the significance of the spheroidsMARY-Xmodel in drug screening and underscore the potential of the CGX motif as a promising anticancer pharmacophore.

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