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Advances in Brief

Enhanced Efficacy of Combinations of Retinoic Acid- and Retinoid X Receptor-selective Retinoids and α-Interferon in Inhibition of Cervical Carcinoma Cell Proliferation

Reuben Lotan, Marcia I. Dawson, Chang-Chun Zou, Ling Jong, Dafna Lotan and Chang-Ping Zou
Reuben Lotan
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Marcia I. Dawson
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Chang-Chun Zou
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Ling Jong
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Dafna Lotan
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Chang-Ping Zou
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DOI:  Published January 1995
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Abstract

Retinoic acid receptors and retinoid X receptors form heterodimers, bind to retinoic acid response elements, and transactivate the transcription of retinoid-responsive genes. Two synthetic retinoids [4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoic acid (TTAB) and 6-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2-naphthalenecarboxylic acid (TTNN)], which preferentially bind retinoic acid receptors, inhibited the proliferation of cervical carcinoma ME180 cells by 50% at 0.2 nm and 0.2 µm, respectively. In contrast, two other retinoids [2-(4-carboxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1,3-dithiane (SR11203) and 4-(2-methyl-1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)propenyl)benzoic acid (SR11217)], which preferentially bind retinoic X receptors, inhibited growth by only 12 and 18% at 1 µm, respectively. The combination of suboptimal concentrations of TTAB (0.1 nm) or TTNN (10 nm) with each of the retinoic X receptor-selective retinoids at 1 µm showed more than additive effects on cell proliferation, especially with SR11217. Further increases in proliferation inhibition were observed when IFN-α (100 units/ml) was added to these retinoid combinations. Activation of transcription of a reporter gene linked 3′ to the retinoic acid receptor β retinoic acid response element in transiently transfected cells also exhibited additive effects when the cells were treated with combinations of TTAB or TTNN with SR11217. This additive activation of transcription may be the reason why the combination of retinoids is more effective than each retinoid alone. The results also suggest that the use of combinations of retinoids and IFN-α may lead to enhanced antitumor effects.

Footnotes

  • ↵1 Supported by USPHS Grants P30 CA16672-18 [R. L.] and P01 CA51993 [M. I. D.] from the National Cancer Institute and by the Abell-Hanger Foundation Professorship [R. L.].

  • ↵2 To whom requests for reprints should be addressed, at Department of Tumor Biology, Box 108, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

  • Received November 15, 1994.
  • Accepted November 30, 1994.
  • ©1995 American Association for Cancer Research.
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January 1995
Volume 55, Issue 2
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Enhanced Efficacy of Combinations of Retinoic Acid- and Retinoid X Receptor-selective Retinoids and α-Interferon in Inhibition of Cervical Carcinoma Cell Proliferation
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Enhanced Efficacy of Combinations of Retinoic Acid- and Retinoid X Receptor-selective Retinoids and α-Interferon in Inhibition of Cervical Carcinoma Cell Proliferation
Reuben Lotan, Marcia I. Dawson, Chang-Chun Zou, Ling Jong, Dafna Lotan and Chang-Ping Zou
Cancer Res January 15 1995 (55) (2) 232-236;

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Enhanced Efficacy of Combinations of Retinoic Acid- and Retinoid X Receptor-selective Retinoids and α-Interferon in Inhibition of Cervical Carcinoma Cell Proliferation
Reuben Lotan, Marcia I. Dawson, Chang-Chun Zou, Ling Jong, Dafna Lotan and Chang-Ping Zou
Cancer Res January 15 1995 (55) (2) 232-236;
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