Abstract
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.
Highlights
With 174,650 new cases diagnosed in 2018, prostate cancer is the most common cancer in men in the United States [1]
Consistent with what has been observed in the literature, treatment with α-TOC elicited virtually no effect on cell viability [34] (Figure 1A). α-tocopherol ether butyrate (α-TEB) had no effect on with no effect on celland viability
Combination chemotherapy has been used for years; that the administration of standard chemotherapeutic drugs is often accompanied by debilitating toxic side effects remains a noteworthy obstacle in cancer treatment
Summary
With 174,650 new cases diagnosed in 2018, prostate cancer is the most common cancer in men in the United States [1]. Of those diagnosed with prostate cancer, 10–20% will develop the more aggressive castration-resistant prostate cancer (CRPC) within 4–5 years, and more than 84% of those diagnosed with CRPC have metastatic cancer at the time of diagnosis [2]. Most prostate cancers begin androgen-sensitive and can be treated with androgen-deprivation therapy; cases of advanced prostate cancer frequently become castration-resistant after 2–3 years of regular treatment [5,6]. Prostate cancer frequently becomes resistant to common chemotherapeutic
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