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Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer

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Abstract

Purpose

To examine the effect of bicalutamide and embelin on the growth of prostate cancer cells in vitro and in vivo

Methods

Cell viability was determined by MTT assay. Micelles were fabricated with polyethylene glycol-b-polylactic acid (PEG-PLA) copolymer and characterized in terms of particle size, micellar solubilization and drug loading, followed by evaluation in nude mice bearing LNCaP xenografts.

Results

Embelin induced caspase 3 and 9 activation in LNCaP and C4–2 cells by decreasing XIAP expression and was more potent than bicalutamide in killing prostate tumor cells irrespective of their androgen status. As analyzed by isobologram analysis the combination of bicalutamide and embelin was synergistic for C4–2 but additive and slightly antagonistic for LNCaP cells. Micellar formulation resulted in at least 60-fold increase in the aqueous solubility of bicalutamide and embelin. Tumor growth was effectively regressed upon treatment with bicalutamide, but the extent of tumor regression was significantly higher when bicalutamide was formulated in micelles. However, tumor response to bicalutamide stopped after prolonged treatment and began to grow. Sequential treatment with XIAP inhibitor embelin resulted in regression of these hormone refractory tumors.

Conclusion

Combined treatment with bicalutamide and embelin may be an effective strategy for treating hormone refractory prostate cancer.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 19 South Manassas (Room 224), Memphis, Tennessee, 38103-3308, USA

    Michael Danquah, Feng Li, Charles B. Duke III, Duane D. Miller & Ram I. Mahato

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  1. Michael Danquah
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  2. Feng Li
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  3. Charles B. Duke III
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  4. Duane D. Miller
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  5. Ram I. Mahato
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Correspondence to Ram I. Mahato.

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Danquah, M., Li, F., Duke, C.B. et al. Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer. Pharm Res 26, 2081–2092 (2009). https://doi.org/10.1007/s11095-009-9903-5

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  • DOI: https://doi.org/10.1007/s11095-009-9903-5

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