RESUMO
Curcumin has been used as a traditional medicine and/or functional food in several cultures because of its health benefits including anticancer properties. However, poor oral bioavailability of curcumin has limited its oral usage as a food supplement and medical food. Here we formulated curcumin pellets using a solid dispersion technique. The pellets had the advantages of reduced particle size, improved water solubility, and particle porosity. This pellet form led to an improvement in curcumin's oral bioavailability. Additionally, we used the C-Map and Library of Integrated Network-Based Cellular Signatures (LINCS) Unified Environment (CLUE) gene expression database to determine the potential biological functions of formulated curcumin. The results indicated that, similar to conventional curcumin, the formulated curcumin acted as an NF-κB pathway inhibitor. Moreover, ConsensusPathDB database analysis was used to predict possible targets and it revealed that both forms of curcumin exhibit similar biological functions, including apoptosis. Biochemical characterization revealed that both the forms indeed induced apoptosis of hepatocellular carcinoma (HCC) cell lines. We concluded that the formulated curcumin increases the oral bioavailability in animals, and, as expected, retains characteristics similar to conventional curcumin at the cellular level. Our screening platform using big data not only confirms that both the forms of curcumin have similar mechanisms but also predicts the novel mechanism of the formulated curcumin.
Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Aurora Quinase A/efeitos dos fármacos , Disponibilidade Biológica , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Sorafenibe/administração & dosagemRESUMO
Withania somnifera extracts are known for their anti-cancerous, anti-inflammatory and antioxidative properties. One of their mechanisms of actions is to modulate mitochondrial function through increasing oxidative stress. Recently 'priming' has been suggested as a potential mechanism for enhancing cancer cell death. In this study we demonstrate that 'priming', in HT-29 colon cells, with W. somnifera root extract increased the potency of the chemotherapeutic agent cisplatin. We have also showed the W. somnifera root extract enhanced mitochondrial dysfunction and that the underlying mechanism of 'priming' was selectively through increased ROS. Moreover, we showed that this effect was not seen in non-cancerous cells.