Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells

  • Authors:
    • C. Herold
    • M. Ganslmayer
    • M. Ocker
    • M. Hermann
    • E. G. Hahn
    • D. Schuppan
  • View Affiliations

  • Published online on: January 1, 2002     https://doi.org/10.3892/ijo.20.1.89
  • Pages: 89-96
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Abstract

Chemotherapy does not have a prominent role in the treatment of hepatoma. However, an acyclic retinoid prevented tumor recurrence post-hepatectomy, and tamoxifen (TAM) induced apoptosis in tumor cells. Combination therapy of these agents on proliferation and apoptosis of hepatoma cells has not been explored. HepG2, Hep1B, Hepa1-6 and MH1C1 hepatoma cells were incubated with TAM, 9-cis- and all-trans retinoic acid (CRA, ATRA, respectively) alone or in combination. Proliferation rate was assessed and apoptosis was analyzed by flow cytometry, immunostaining, caspase activity assays and the expression of apoptosis- and/or cell cycle-related molecules. CRA and TAM, but not ATRA monotherapy were moderately effective. Apoptosis was accompanied by upregulation of caspase 3 and 8 activity, and increased p27, bax, caspase 3 expression, while the levels of p21cip/waf and bcl-2 were unchanged or decreased. Combination therapy enhanced apoptosis from a maximum of 60% after monotherapy to more than 90% after 96 h in all cell types. Pro-apoptotic effects were paralleled by inhibition of proliferation. Combination of TAM and CRA, but not ATRA, have an additive to synergistic anti-proliferative and pro-apoptotic effect on HCC cells. This justifies trials for HCC using combinations of these biological response modifiers.

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January 2002
Volume 20 Issue 1

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

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APA
Herold, C., Ganslmayer, M., Ocker, M., Hermann, M., Hahn, E.G., & Schuppan, D. (2002). Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells. International Journal of Oncology, 20, 89-96. https://doi.org/10.3892/ijo.20.1.89
MLA
Herold, C., Ganslmayer, M., Ocker, M., Hermann, M., Hahn, E. G., Schuppan, D."Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells". International Journal of Oncology 20.1 (2002): 89-96.
Chicago
Herold, C., Ganslmayer, M., Ocker, M., Hermann, M., Hahn, E. G., Schuppan, D."Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells". International Journal of Oncology 20, no. 1 (2002): 89-96. https://doi.org/10.3892/ijo.20.1.89