Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments, and the administration of chemotherapeutic drugs is often accompanied by toxic side effects. Combination therapy is one tool that can be used to combat therapeutic resistance and drug toxicity. Vitamin E (VE) compounds and analogs have been proposed as potential non-toxic chemotherapeutics. Here we modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to determine whether combinations of three chemotherapeutic agents: γ-tocotrienol (γ-T3), α-tocopherol ether acetate (α-TEA), and docetaxel (DOC), would prove more effective than docetaxel alone in the treatment of human prostate cancer cells. Response surfaces were generated for cell viability, and the optimal treatment combination for reducing cell viability was calculated. We found that a combination of 20 µM γ-T3, 30 µM α-TEA, and 25 nm DOC was most effective in the treatment of PC-3 cells. We also found that the combination of γ-T3 and α-TEA with DOC decreased the amount of DOC required to reduce cell viability in PC-3 cells and ameliorated therapeutic resistance in DOC-resistant PC-3 cells.

Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments. Moreover, the administration of conventional chemotherapeutic drugs, such as docetaxel (DOC), poses the risk of debilitating toxic side effects. Combination chemotherapy, in which several compounds targeting multiple cellular pathways are administered jointly, is one tool that can be used to combat therapeutic resistance and drug toxicity. Vitamin E (VE) compounds and analogs have been proposed as potential non‐toxic chemotherapeutics. We modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to determine whether combinations of three chemotherapeutic agents (γ‐tocotrienol (γ‐T3), α‐tocopherol ether acetate (α‐TEA), and DOC) would prove more effective than DOC alone in the treatment of PC‐3 and DU145 human prostate cancer cells. A response surface was generated for cell viability, and the optimal treatment combination for reducing PC‐3 cell viability was calculated. We found that a combination of 30 μM α‐TEA, 20 μM γ‐T3, and 25 nm DOC was most effective in the treatment of PC‐3 cells. We also found that combining γ‐T3 and α‐TEA with DOC decreased the dose of DOC required to significantly reduce cell viability in PC‐3 and DU145 cells. Further, combination treatment consisting of α‐TEA, γ‐T3, and DOC induced apoptosis in PC‐3 cells as evidenced by upregulation of caspases 3 and 7. Finally, we found that combining γ‐T3 and α‐TEA with DOC enhanced treatment efficacy in DOC‐resistant PC‐3 cells. Support or Funding Information Brigham Young University College Undergraduate Research AwardBryant Adams