Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening
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Maria A. Theodoraki1, Celso O. Rezende Jr.2, Oraphin Chantarasriwong2,3, Adriana D. Corben4, Emmanuel A. Theodorakis2 and Mary L. Alpaugh2,5
1Department of Biology, Arcadia University, Philadelphia, PA, USA
2Department of Chemistry and Biochemistry, University of California – San Diego, La Jolla, CA, USA
3Department of Chemistry, Faculty of Science, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand
4Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
5Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Mary L. Alpaugh, e-mail: [email protected]
Emmanuel A. Theodorakis, e-mail: [email protected]
Keywords: drug screening, lymphovascular embolus (LVE), natural products, garcinia xanthone motif (CGX), breast cancer
Received: February 16, 2015 Accepted: June 08, 2015 Published: June 18, 2015
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.
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