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    Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated MDR1, drug efflux and side-population positive and decreased BCL2-family member expression

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    Author
    Steelman, Linda S.; Abrams, Stephen L.; Ruvolo, Peter; Ruvolo, Vivian; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M.; Neri, Luca M.; Candido, Saverio; Libra, Massimo; McCubrey, James A.
    Abstract
    Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/ Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/ Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA). Elevated MDR1 but not MRP1 mRNA transcripts were detected by quantitative RT-PCR in the drug-resistant cells while transcripts encoding anti-apoptotic genes such as: BCL2, BCLXL and MCL1 were observed at higher levels in the drug-sensitive FL5.12 cells. The percentage of cells that were side-population positive was increased in the drug-resistant cells compared to the parental line. Drug-resistance and side- positive population cells have been associated with cancer stem cells (CSC). Our studies suggest mechanisms which could allow the targeting of these molecules to prevent drug-resistance.
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    http://hdl.handle.net/10342/8176
    Date
    2017-12-06
    Citation:
    APA:
    Steelman, Linda S., & Abrams, Stephen L., & Ruvolo, Peter, & Ruvolo, Vivian, & Cocco, Lucio, & Ratti, Stefano, & Martelli, Alberto M., & Neri, Luca M., & Candido, Saverio, & Libra, Massimo, & McCubrey, James A.. (December 2017). Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated MDR1, drug efflux and side-population positive and decreased BCL2-family member expression. , (), - . Retrieved from http://hdl.handle.net/10342/8176

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    MLA:
    Steelman, Linda S., and Abrams, Stephen L., and Ruvolo, Peter, and Ruvolo, Vivian, and Cocco, Lucio, and Ratti, Stefano, and Martelli, Alberto M., and Neri, Luca M., and Candido, Saverio, and Libra, Massimo, and McCubrey, James A.. "Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated MDR1, drug efflux and side-population positive and decreased BCL2-family member expression". . . (), December 2017. September 27, 2023. http://hdl.handle.net/10342/8176.
    Chicago:
    Steelman, Linda S. and Abrams, Stephen L. and Ruvolo, Peter and Ruvolo, Vivian and Cocco, Lucio and Ratti, Stefano and Martelli, Alberto M. and Neri, Luca M. and Candido, Saverio and Libra, Massimo and McCubrey, James A., "Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated MDR1, drug efflux and side-population positive and decreased BCL2-family member expression," , no. (December 2017), http://hdl.handle.net/10342/8176 (accessed September 27, 2023).
    AMA:
    Steelman, Linda S., Abrams, Stephen L., Ruvolo, Peter, Ruvolo, Vivian, Cocco, Lucio, Ratti, Stefano, Martelli, Alberto M., Neri, Luca M., Candido, Saverio, Libra, Massimo, McCubrey, James A.. Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated MDR1, drug efflux and side-population positive and decreased BCL2-family member expression. . December 2017; (): . http://hdl.handle.net/10342/8176. Accessed September 27, 2023.
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