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Inhibition of acid ceramidase by a 2-substituted aminoethanol amide synergistically sensitizes prostate cancer cells to N-(4-hydroxyphenyl) retinamide by Valérie Gouazé-Andersson; Margaret Flowers; Ramin Karimi; Gemma Fabriás; Antonio Delgado; Josefina Casas; Myles C. Cabot is a Medicine article available to read on EtoBox.

## Abstract ## BACKGROUND The purpose of this study was to determine whether the therapeutic efficacy of fenretinide (4‐HPR), a ceramide‐generating anticancer agent, could be enhanced in prostate cancer cells by inclusion of a novel synthetic acid ceramidase (AC) inhibitor, DM102, a pivaloylamide of a 2‐substituted aminoethanol. In prostate cancer, AC plays a role in progression and resistance to chemotherapy. ## METHODS PC‐3 and DU 145 hormone‐refractory human prostate cancer cell lines were used. Cells were exposed to 4‐HPR, DM102, and combinations; viability, apoptosis, cell migration, ceramide metabolism, and levels of reactive oxygen species (ROS) were assessed. ## RESULTS Single agent 4‐HPR and DM102 (2.5–10 μM) were weakly cytotoxic; however, combinations synergistically decreased cell viably to as low as 1.5% of control. N‐oleoylethanolamine (NOE), a frequently employed AC inhibitor, was not effective in producing synergy. The 4‐HPR/DM102 regimen enhanced caspase activity and increased [^3^H](dihydro)ceramide and ROS levels 6‐ and 30‐fold over control, respectively. The antioxidant vitamin E, but not the de novo ceramide synthesis inhibitor myriocin, partially rescued cells

Author

Valérie Gouazé-Andersson; Margaret Flowers; Ramin Karimi; Gemma Fabriás; Antonio Delgado; Josefina Casas; Myles C. Cabot

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0270-4137)

Published

2010

Language

EN

Field

Medicine (Health Sciences)