Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening.
Oncotarget
; 6(25): 21255-67, 2015 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-26101913
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 spheroids(MARY-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 spheroids(MARY-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 spheroids(MARY-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 spheroids(MARY-X) model in drug screening and underscore the potential of the CGX motif as a promising anticancer pharmacophore.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Screening Assays, Antitumor
/
Spheroids, Cellular
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Drug Evaluation, Preclinical
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Neoplasms
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Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2015
Type:
Article
Affiliation country:
United States