Abstract 1700: A combination of two tropical spice compounds potentiates chemotherapy response in castration-resistant prostate cancer cells

Abstract

Abstract Introduction: Patients with castration resistant advanced prostate cancer (CRPC) respond poorly to potent chemotherapeutic drugs (e.g., Docetaxel or Mitoxantrone) with survival advantages that last less than 4 months. Since chemotherapy itself has morbidity in the elderly patients, adding another such drug is unlikely to improve the outcome. We investigated the potential therapeutic benefits of treating CRPC with a combination of two natural dietary anti-proliferative compounds: Curcumin and Piperine. They are derived from the tropical spices, turmeric and black pepper, respectively. Both are orally bioavailable and can be consumed over a long period of time. Materials and methods: The cytotoxicity of Curcumin, Piperine, and Docetaxel were individually tested on a CRPC cell line PC-3, which was incubated for 48 hours or 72 hours. Cytotoxicity was evaluated by cell counting, a colorimetric assay and by clonogenic survival, colony-formation assay. Enhancement of Docetaxel cytotoxicity by natural compounds was evaluated by treating cells with these compounds 24 hours before adding Docetaxel or with co-incubation. The potential mechanism of cytotoxicity was examined by an apoptosis assay and changes in cell cycle phase-fractions. The efficacy of the combination was evaluated by Isobologram analysis and ANOVA. Results: All three drugs tested on PC-3 showed cytotoxicity, Docetaxel was the most cytotoxic (IC50∼ 25 nM) and Piperine was the least cytotoxic (IC50∼ 100 μM). Curcumin alone was significantly cytotoxic to PC-3 cells at 10 μM but it enhanced the cytotoxicity of Docetaxel. Piperine, when combined with Curcumin or Docetaxel, significantly increased the cytotoxicity by 50%. Prior exposure to Piperine resulted in enhanced cytotoxicity of Docetaxel and Curcumin more than when in co-incubation. The increased cytotoxicity in combination therapy was mainly due to increased apoptotic activity. Conclusion: This study demonstrated that combining diet-derived antiproliferatinve compounds with a chemotherapy drug can potentially enhance tumoricidal activity and therefore, potentially reduce morbidity and mortality of patients with CRPC. Pretreatment with dietary compounds could potentially enhance subsequent treatment with chemotherapy agents. Citation Format: Taaha A. Mendha, Shamaladevi Nagarajarao, Balakrisha L. Lokeshwar. A combination of two tropical spice compounds potentiates chemotherapy response in castration-resistant prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1700. doi:10.1158/1538-7445.AM2014-1700