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Combined effects of curcumin and doxorubicin on cell death and cell migration of SH-SY5Y human neuroblastoma cells

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Abstract

Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the influences of curcumin on survival, apoptosis, migration, and its combined effects with doxorubicin were investigated in SH-SY5Y cells by cell survival assay, flow cytometry, migration assays, and RT-PCR. Curcumin inhibited SH-SY5Y cell growth and induced apoptosis in dose- and time-dependent manners. This apoptotic induction relied on the upregulation of p53 and p21. Moreover, the treatment of curcumin for 24 h significantly suppressed cell migration, together with the downregulation of matrix metalloproteinase-2 (MMP-2) and upregulation of tissue inhibitor of metalloproteinases-1 (TIMP-1). The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Pretreatment with curcumin increased the fraction of doxorubicin-induced apoptotic cells from 21.76 ± 0.50 to 57.74 ± 2.68%. Co-treatment with doxorubicin plus curcumin further inhibited 3D tumor migration. Altogether, the results suggest that curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved.

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Funding

This work was supported by the National Research Council of Thailand (NRCT), Suranaree University of Technology (SUT), and Office of the Higher Education Commission under the NRU Project of Thailand.

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  1. Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima, 30000, Thailand

    Jirapat Namkaew, Thiranut Jaroonwitchawan, Narawadee Rujanapun, Jantip Saelee & Parinya Noisa

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  1. Jirapat Namkaew
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  2. Thiranut Jaroonwitchawan
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  3. Narawadee Rujanapun
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  4. Jantip Saelee
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  5. Parinya Noisa
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Contributions

Conceived and designed the study, Parinya Noisa; performed the biological experiments, Jirapat Namkaew, Thiranut Jaroonwitchawan, Narawadee Rujanapun, and Jantip Saelee; statistical analysis, Jirapat Namkaew and Thiranut Jaroonwitchawan; provided resources, Narawadee Rujanapun; wrote the paper, Parinya Noisa and Thiranut Jaroonwitchawan. All authors read and proofed the final manuscript.

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Correspondence to Parinya Noisa.

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Editor: Tetsuji Okamoto

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Namkaew, J., Jaroonwitchawan, T., Rujanapun, N. et al. Combined effects of curcumin and doxorubicin on cell death and cell migration of SH-SY5Y human neuroblastoma cells. In Vitro Cell.Dev.Biol.-Animal 54, 629–639 (2018). https://doi.org/10.1007/s11626-018-0288-9

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