In vitro effect of carboplatin, cytarabine, paclitaxel, vincristine, and low-power laser irradiation on murine mesenchymal stem cells.
OBJECTIVE
Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Cytostatics can decrease, but low-power laser irradiation (LPLI) can increase the growth of MSCs. The interaction of LPLI, MSCs and cytostatics is not known. This study investigated the effect of four cytostatics (carboplatin, cytarabine, paclitaxel, vincristine), LPLI, and combination of a cytostatic drug and LPLI on murine MSCs (mMSCs).


METHODS
MMSCs were exposed to LPLI (660 nm diode laser; 60 mW output power; range of power density: 76-156 mW/cm(2); range of energy density: 1.9-11.7 J/cm(2)) and/or a cytostatic drug (carboplatin: 2, 10, 50; cytarabine: 0.4, 10, 50; paclitaxel: 0.4, 2, 10; vincristine: 0.02, 0.1, 0.5 microg/ml, respectively). Cell proliferation was measured after 24, 48, or 72 hours incubation.


RESULTS
LPLI at 1.9 J/cm(2) dose increased the proliferation rate with 41% after 48 hours. However, 11.7 J/cm(2) LPLI caused 42% inhibition and cytostasis was still detectable after 72 hours. LPLI caused equivalent stimulation in single or in divided doses (3.8 vs. double 1.9 J/cm(2) in a 24-hour period). The cytotoxicity of 50 microg/ml carboplatin was eliminated, the inhibitory power of 0.1 microg/ml vincristine was attenuated by 1.9 J/cm(2) LPLI even 3 days post-treatment (attenuation >10%). The 11.7 J/cm(2) LPLI enhanced the cytotoxicity of 50 microg/ml cytarabine (from 48% to 73%) and 10 microg/ml paclitaxel (from 37% to 78%). Combination of the ineffective 0.4 microg/ml cytarabine or paclitaxel with the inhibitory 11.7 J/cm(2) LPLI exhibited stronger inhibition than the 11.7 J/cm(2) LPLI alone (69% and 69% vs. 42%).


CONCLUSIONS
Low energy density of LPLI increases and high energy density of LPLI decreases the proliferation of mMSCs. Furthermore, LPLI can prevent or attenuate some drug's cytotoxicity and amplify others'. The result depends on the applied energy density, on the type and concentration of the cytostatics.
Horvát-Karajz
Károly
K
Second Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary. karoly.horvat-karajz@oncology.hu
Balogh
Zsuzsanna
Z
Kovács
Viktória
V
Drrernat
András Hámori
AH
Sréter
Lídia
L
Uher
Ferenc
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D018929:Cell Culture Techniques; D003561:Cytarabine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D054023:Lasers, Semiconductor; D028022:Low-Level Light Therapy; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D016190:Carboplatin; D017239:Paclitaxel