RARα is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells

  • Authors:
    • Shiro Jimi
    • Kota Mashima
    • Taichi Matsumoto
    • Shuji Hara
    • Junji Suzumiya
    • Kazuo Tamura
  • View Affiliations

  • Published online on: August 1, 2007     https://doi.org/10.3892/ijo.31.2.397
  • Pages: 397-404
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Abstract

Retinoids are used for treatment of acute promyelocytic leukemia (APL). Am-80, Tamibarotene, binds to retinoic acid receptor alpha (RARα) more specifically than all-trans retinoic acid. We studied the tumor cell suppressive effects of Am-80, with respect to cytotoxicity and growth inhibition using eight myeloid and lymphoid malignant cells in culture (HL-60, HL-60R, K-562, Kasumi-1, MEG01, Raji, U266B1, and U937). The effects of Am-80 were examined during 9 days of incubation with 10−7-10−5 M of Am-80 in culture medium, which was changed every 3 days. HL-60 were the only cells sensitive to Am-80-induced cytotoxicity; the latter reached more than 95% after 9 days of incubation, and death was primarily through apoptosis. The total mass of RARα in HL-60 was significantly greater (p<0.006) than in ATRA-resistant HL-60 (HL-60R) as well as all of other cells tested. However, in all cells excluding HL-60, Am-80 induced time- and dose-dependent cell growth inhibition without noticeable cytotoxicity. TGF-β2 was released into the media containing cells incubated with Am-80 for 3 days. A dose-dependent increment of phosphorylation of Smad-2 was also detected. The relative amount of secreted TGF-β2 correlated with the growth inhibition rates in all cells tested excluding HL-60, and with the total mass of RARα in the cells (p=0.0137). Our results indicate that Am-80-induced cell-type non-specific growth inhibition is mediated by TGF-β2, where the total mass of RARα could be an important regulatory factor in hematologic malignant cells.

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August 2007
Volume 31 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Jimi S, Mashima K, Matsumoto T, Hara S, Suzumiya J and Tamura K: RARα is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells. Int J Oncol 31: 397-404, 2007
APA
Jimi, S., Mashima, K., Matsumoto, T., Hara, S., Suzumiya, J., & Tamura, K. (2007). RARα is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells. International Journal of Oncology, 31, 397-404. https://doi.org/10.3892/ijo.31.2.397
MLA
Jimi, S., Mashima, K., Matsumoto, T., Hara, S., Suzumiya, J., Tamura, K."RARα is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells". International Journal of Oncology 31.2 (2007): 397-404.
Chicago
Jimi, S., Mashima, K., Matsumoto, T., Hara, S., Suzumiya, J., Tamura, K."RARα is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells". International Journal of Oncology 31, no. 2 (2007): 397-404. https://doi.org/10.3892/ijo.31.2.397