1. γ-Tocotrienol and α-Tocopherol Ether Acetate Enhance Docetaxel Activity in Drug-Resistant Prostate Cancer Cells
- Author
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Andrew Graham, Jason Kenealey, Spencer Asay, Sydney Hollingsworth, Bradley Barnes, David J. Michaelis, and Richard Oblad
- Subjects
Male ,Combination therapy ,Cell Survival ,alpha-Tocopherol ,Pharmaceutical Science ,Antineoplastic Agents ,Docetaxel ,Ether ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,lcsh:Organic chemistry ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Viability assay ,Chromans ,Physical and Theoretical Chemistry ,030304 developmental biology ,0303 health sciences ,combination chemotherapy ,Dose-Response Relationship, Drug ,Organic Chemistry ,mixture design response surface methodology ,Prostatic Neoplasms ,Cancer ,Drug Synergism ,Combination chemotherapy ,vitamin e ,medicine.disease ,prostate cancer ,chemistry ,Drug Resistance, Neoplasm ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Molecular Medicine ,Tocotrienol ,medicine.drug - 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: &gamma, tocotrienol (&gamma, T3), &alpha, tocopherol ether acetate (&alpha, 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 µ, M &gamma, T3, 30 µ, M &alpha, TEA, and 25 nm DOC was most effective in the treatment of PC-3 cells. We also found that the combination of &gamma, T3 and &alpha, 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.
- Published
- 2020