Abstract A20: Differential rates of proliferation and apoptosis observed in human cutaneous T-cell lymphoma cell lines, in response to treatment with 9-cis UAB30, a novel rexinoid analog

Abstract

Abstract Cutaneous T-cell lymphoma (CTCL) designates a heterogeneous group of malignancies, characterized by the infiltration and detection of transformed T-cell lymphocytes in the skin. Although there is no cure for CTCL, a wide range of treatment options have been developed for use in the clinical setting. Bexarotene, a retinoid X receptor (RXR) agonist or rexinoid, is a commonly used treatment modality for CTCL. However, documented increases in the levels of triglycerides of CTCL patients, resulting from treatment with bexarotene, point to concerns over the long-term use and efficacy of this anticancer agent. We have recently synthesized a novel rexinoid, 9-cis UAB30, which does not elevate triglycerides in vivo and have begun evaluating its use as a potential chemotherapeutic agent for the treatment of CTCL. In this study, we compared the efficacy of 9-cis UAB30 to that of bexarotene in reducing cell proliferation and inducing apoptosis, in the three human CTCL cell lines HH, MJ, and Hut78. A standard XTT assay was used to determine the rate of cell proliferation of CTCL cells. In all three lines, 9-cis UAB30 was equally and sometimes more effective than bexarotene at suppressing cell proliferation. Using an annexin V binding assay, we next analyzed the rate of apoptosis in these human CTCL lines. Interestingly, we observed the MJ cell line to be resistant to apoptosis, when treated with either compound. The HH cell line exhibited a similar increase in apoptosis, whether treated with 9-cis UAB30 or bexarotene. Finally, the Hut78 cell line showed a greater sensitivity to apoptosis, when treated with 9-cis UAB30 as compared to bexarotene. Taken together, these preliminary results indicate that 9-cis UAB30 appears to be equally if not more effective than bexarotene at suppressing cell proliferation and appears to exert differential effects on the rate of apoptosis that may be cell-line specific. These differential responses of human CTCL cells have implications for the development of next-generation, rexinoid-based therapies and reveal that 9-cis UAB30 may be a better alternative for the treatment of CTCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A20.