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

Maria A. Theodoraki, Celso O. Rezende, Oraphin Chantarasriwong, Adriana D. Corben, Emmanuel A. Theodorakis, Mary L. Alpaugh

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)21255-21267
Number of pages13
JournalOncotarget
Volume6
Issue number25
DOIs
StatePublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology

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