title: Human mesenchymal stem cells are resistant to Paclitaxel by adopting a non-proliferative fibroblastic state.
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.
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America.
authors.forename: Dale B
authors.initials: DB
authors.lastname: Bosco
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
authors.forename: Rachael
authors.initials: R
authors.lastname: Kenworthy
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
authors.forename: Diego A R
authors.initials: DA
authors.lastname: Zorio
authors.affiliation: 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.
authors.forename: Qing-Xiang Amy
authors.initials: QX
authors.lastname: Sang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel