Micellar delivery of bicalutamide and embelin for treating prostate cancer

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

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2081-2092
Number of pages12
JournalPharmaceutical Research
Volume26
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

Keywords

  • Androgen
  • Bicalutamide
  • Embelin
  • Micelles
  • Prostate cancer

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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