Human mesenchymal stem cells are resistant to Paclitaxel by adopting a non-proliferative fibroblastic state

Dale B Bosco; Rachael Kenworthy; Diego A R Zorio; Qing-Xiang Amy Sang

doi:10.1371/journal.pone.0128511

Human mesenchymal stem cells are resistant to Paclitaxel by adopting a non-proliferative fibroblastic state

PLoS One. 2015 Jun 1;10(6):e0128511. doi: 10.1371/journal.pone.0128511. eCollection 2015.

Authors

Dale B Bosco¹, Rachael Kenworthy², Diego A R Zorio², Qing-Xiang Amy Sang³

Affiliations

¹ Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America.
² Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
³ Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.

Abstract

Human mesenchymal stem cell (hMSC) resistance to the apoptotic effects of chemotherapeutic drugs has been of major interest, as these cells can confer this resistance to tumor microenvironments. However, the effects of internalized chemotherapeutics upon hMSCs remain largely unexplored. In this study, cellular viability and proliferation assays, combined with different biochemical approaches, were used to investigate the effects of Paclitaxel exposure upon hMSCs. Our results indicate that hMSCs are highly resistant to the cytotoxic effects of Paclitaxel treatment, even though there was no detectable expression of the efflux pump P-glycoprotein, the usual means by which a cell resists Paclitaxel treatment. Moreover, Paclitaxel treatment induces hMSCs to adopt a non-proliferative fibroblastic state, as evidenced by changes to morphology, cellular markers, and a reduction in differentiation potential that is not directly coupled to the cytoskeletal effects of Paclitaxel. Taken together, our results show that Paclitaxel treatment does not induce apoptosis in hMSCs, but does induce quiescence and phenotypic changes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Adipocytes / cytology
Adipocytes / drug effects
Antineoplastic Agents, Phytogenic / metabolism
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Differentiation / drug effects
Cell Proliferation / drug effects*
Fibroblasts / cytology
Fibroblasts / drug effects
Humans
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / drug effects*
Paclitaxel / metabolism
Paclitaxel / pharmacology*
Protein Binding

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents, Phytogenic
Paclitaxel

Grants and funding

This work was supported by internal grants from Florida State University. Bosco and Sang salaries are supported by Florida State University; Kenworthy and Zorio salaries are supported by the Florida State University Research Foundation. This work was supported in part by an Endowed Professorship in Cancer Research to Dr. Sang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.