Abstract
New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN) having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, and environmental, genetic and epigenetic factors are involved in its carcinogenesis [1,2,3]
It was observed that the encapsulation of omega-3 PUFA into the solid lipid nanoparticles (SLN) enhanced significantly their incorporation in human HT-29 colorectal cancer (CRC) cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation
Plenty of studies performed both in vitro and in vivo in different kinds of cancer have demonstrated the ability of these fatty acids to inhibit cell proliferation and induce apoptosis [16,17,18,19,20,21,22,23,24] These fatty acids have been some positive associations were recently found between the incidence/progression of human prostate cancer and high levels of intake or high concentrations of these fatty acids (FA) in blood or prostate tissue [25]
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, and environmental, genetic and epigenetic factors are involved in its carcinogenesis [1,2,3]. Plenty of studies performed both in vitro and in vivo in different kinds of cancer have demonstrated the ability of these fatty acids to inhibit cell proliferation and induce apoptosis [16,17,18,19,20,21,22,23,24] These fatty acids have been some positive associations were recently found between the incidence/progression of human prostate cancer and high levels of intake or high concentrations of these fatty acids (FA) in blood or prostate tissue [25]. The potential dangerousness of extremely high levels of omega-3 PUFA has been generally related to their unsaturated structure, which makes them highly susceptible to oxidation This may result into reduced bioactivity, and cell oxidative stress, that may induce toxic and carcinogenic effects [11]. This possibility cannot be ignored, and for a potential application of these FA in the adjuvant therapy of CRC, it would be important to supply colonic mucosa cells with relatively moderate concentrations of these FA, that, should still result able to inhibit CRC cell growth
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