Plant-based omega-3 stearidonic acid enhances antitumor activity of doxorubicin in human prostate cancer cell lines
Journal Title: Journal of Cancer Research & Therapy - Year 2014, Vol 2, Issue 9
Abstract
Doxorubicin (DOX) is a first choice cytostatic drug in treatment of many cancers but among its side effects is cardiac toxicity. Stearidonic omega-3 fatty acid (SDA) has cardiac protective qualities and, therefore, we investigated the combinatory effects of DOX and SDA on proliferation/viability in the human prostate cancer (PCa) cell lines LNCaP, PC3, and DU145 as well as possible modulatory effects on expression of androgen receptor (AR), peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear transcription factors implicated in tumorigenesis. The median inhibitory effects (IC50) of SDA were 601, 116, 145 µM and that of DOX were 802, 761, 363 nM in LNCaP, PC3 and DU145, respectively. Equipotent combinations of DOX and SDA based on 2-fold dilutions and constant combination ratios derived from the above IC50 values suggested anticancer synergism with a combination index (CI) of less than 1 as determined using the Chou-Talalay method based on the median-effect equation and the mass action law. Stearidonic acid strongly inhibited TNFα-activated NF-κB in stably transduced LNCaP cells. We used immunocytochemistry, real-time PCR, western blotting, and transactivation assays to demonstrate inhibition of agonist-activated AR and PPARγ expression following treatment with DOX and SDA singly or in combination. This study provides proof-of-concept for using DOX and SDA in combination to reduce dose and toxicity of DOX in PCa clinical translation studies.
Authors and Affiliations
Trebelhorn CH, Dennis JC, Pondugula SR, Samuel T, Coleman E, Flannery P, Morrison E, Mansour M
Keywords
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