Abstract
Prostate cancer (PCa) is one of the most common cancers in older men and is associated with high mortality. Despite advances in screening for early detection of PCa, a large proportion of patients continue to be diagnosed with metastatic disease, with ~20% of men showing a high tumor grade and stage. Medicinal plant extracts have a great potential to prevent/treat PCa, as well as to reduce its incidence/prevalence and improve survival rates. One of the most promising extracts is curcumin, which is a major, nontoxic, bioactive compound of Curcuma longa. Curcumin has strong antitumor activity in vitro. However, its potential beneficial in vivo affects are limited by its low intestinal absorption and rapid metabolism. In this study, curcumin was impregnated into a biodegradable poly(lactic-co-glycolic) acid (PLGA) support and characterized by FTIR and DSC, and its release by UV spectrophotometry. PLGA-curcumin was tested in different subcutaneous PCa xenograft models (PC3, 22rv1, and DU145 PCa cell-lines), and its effects evaluated by tumor progression an immuno-histochemical analysis (Trichromic, Ki67 and TUNEL stainings), were compared with those of a commercial curcumin preparation. Our results indicate that curcumin-impregnated PLGA is significantly more active (~2-fold increase) with respect to oral curcumin, which supports its use for subcutaneous administration.
Highlights
Prostate cancer (PCa) is the second largest cancer histotype and the fifth leading cause of cancer-associated deaths in older men worldwide [1,2]
Characterization of poly(lactic-co-glycolic) acid (PLGA) Impregnated with Curcumin in scCO2
The appearance of the most characteristic absorbance band of PLGA corresponding to the carbonyl group (1760 cm−1 ), which increased after impregnation due to the contribution of the C=O group of curcumin
Summary
Prostate cancer (PCa) is the second largest cancer histotype and the fifth leading cause of cancer-associated deaths in older men worldwide [1,2]. Nutrients 2019, 11, 2312 intracellular ROS are critical for proper cellular signaling and homeostatic redox balance, high levels are deleterious and can lead to significant reductions in antioxidant defense mechanisms, which results in DNA, protein, and lipid damage [5,6,7]. Oxidative stress contributes to the initiation and progression of PCa by modulating transcription factors, cell cycle regulators, and DNA [5,8,9]. Against this background, several antioxidant-related phytochemicals have been tested for the prevention/treatment of PCa by ameliorating oxidative stress [10,11,12,13], and some have the added advantage of low toxicity [14]
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