Microtubule-interacting drugs induce moderate and reversible damage to human bone marrow mesenchymal stem cells.
OBJECTIVE
This study aimed to investigate molecular and cellular changes induced in human bone marrow mesenchymal stem cells (hMSCs) after treatment with microtubule-interacting agents and to estimate damage to the bone marrow microenvironment caused by chemotherapy.


METHODS
Using an in vitro hMSC culture system and biochemical and morphological approaches, we studied the effect of nocodazole and taxol(R) on microtubule and nuclear envelope organization, tubulin and p53 synthesis, cell cycle progression and proliferation and death of hMSCs isolated from healthy donors.


CONCLUSIONS
Both nocodazole and taxol reduced hMSC proliferation and induced changes in the microtubular network and nuclear envelope morphology and organization. However, they exhibited only a moderate effect on cell death and partial arrest of hMSCs at G(2) but not at M phase of the cell cycle. Both agents induced expression of p53, exclusively localized in abnormally shaped nuclei, while taxol, but not nocodazole, increased synthesis of beta-tubulin isoforms. Cell growth rates and microtubule and nuclear envelope organization gradually normalized after transfer, in drug-free medium. Our data indicate that microtubule-interacting drugs reversibly inhibit proliferation of hMSCs; additionally, their cytotoxic action and effect on microtubule and nuclear envelope organization are moderate and reversible. We conclude that alterations in human bone marrow cells of patients under taxol chemotherapy are transient and reversible.
Polioudaki
H
H
Department of Biochemistry, School of Medicine, University of Crete, Crete, Greece.
Kastrinaki
M-C
MC
Papadaki
H A
HA
Theodoropoulos
P A
PA
D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology*; D009685:Nuclear Envelope / Q000187:drug effects / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D014404:Tubulin; D050257:Tubulin Modulators; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; D015739:Nocodazole