Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Int J Mol Sci. 2016 Oct 26;17(11):1792. doi: 10.3390/ijms17111792.


Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = -35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners (p ≤ 0.05), at least three to four folds lower IC50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.

Keywords: antiproliferative; apoptosis; biocompatibility; caspase; nanoemulsion; polyphenols; tocopherols; tocotrienols; tumor necrosis factor-α.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Breast / drug effects
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / administration & dosage
  • Curcumin / therapeutic use*
  • Delayed-Action Preparations / chemistry
  • Emulsions / chemistry
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovary / drug effects
  • Ovary / pathology
  • Tocotrienols / administration & dosage
  • Tocotrienols / therapeutic use*
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*


  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Emulsions
  • Tocotrienols
  • Vitamins
  • Curcumin