Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening Journal Article
| Authors: | Theodoraki, M. A.; Rezende, C. O. Jr; Chantarasriwong, O.; Corben, A. D.; Theodorakis, E. A.; Alpaugh, M. L. |
| Article Title: | Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening |
| 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 IC<inf>50</inf> 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 IC<inf>50</inf> 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 IC<inf>50</inf> 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. |
| Keywords: | controlled study; unclassified drug; human cell; cisplatin; doxorubicin; dose response; paclitaxel; methotrexate; antineoplastic agent; apoptosis; bortezomib; breast cancer; gambogic acid; antineoplastic activity; drug structure; in vitro study; drug screening; cancer cell; drug response; drug cytotoxicity; lapatinib; natural products; dissolution; phase 1 clinical trial (topic); xanthone derivative; tumor spheroid; human; article; ic50; garcinia xanthone motif (cgx); lymphovascular embolus (lve); caged garcinia xanthone; mad 28 |
| Journal Title: | Oncotarget |
| Volume: | 6 |
| Issue: | 25 |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Date Published: | 2015-08-25 |
| Start Page: | 21255 |
| End Page: | 21267 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 26101913 |
| DOI: | 10.18632/oncotarget.4013 |
| PMCID: | PMC4673263 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
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