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KMID : 0624620110440010046
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BMB Reports
2011 Volume.44 No. 1 p.46 ~ p.51
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Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin
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Park Jin-Hee
Sihn Choong-Ryoul
Lee Yeon-Su
Lee Sung-Jae
Kim Sang-Hoon
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Abstract
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Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.
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KEYWORD
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Apoptosis, DNA damage, Doxorubicin, Neuroguidin/CANu1
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