RESUMO
Previous studies showed that dopamine (DA) significantly reduces the frequency of cancer stem-like cells (CSC) and enhances the efficacy of sunitinib (SUN) in the treatment of breast cancer and non-small cell lung cancer (NSCLC). To overcome the shortcomings of DA in clinical practice, the purpose of this study was to investigate the efficacy as well as the underlying mechanism of an orally available, N-arylpiperazine-containing compound C2, in the treatment of pancreatic cancer when used alone or in combination with SUN. Our results showed that C2 and SUN exerted synergistic effects on inhibiting the growth of SW1990 and PANC-1 pancreatic cancer cells. C2 significantly inhibited colony formation and migration of both cells. SW1990 xenograft and patient-derived xenograft (PDX) models were utilized for pharmacodynamic investigation in vivo. C2 alone showed little inhibition effect on tumor growth but increased the anti-tumor efficacy of SUN in both xenografts. Moreover, C2 down-regulated CSC markers (CD133 and ALDH) of both cancer cells and up-regulated the expression of dopamine receptor D1 (D1DR) in tumor. Besides, the SW1990 tumor growth was dose-dependently inhibited when the cells were pretreated with C2 before implantation. C2 increased intratumoral cAMP level, and the combination with D1DR specific antagonist SCH23390 reversed the above-mentioned effects of C2 both in vitro and in vivo, indicating the activation of D1DR may be involved in the underlying mechanism of C2 action. In summary, C2 could reduce the CSC frequency and enhance the anti-cancer effect of SUN in the treatment of pancreatic cancer, demonstrating its potential in cancer therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Piperazinas/farmacologia , Receptores de Dopamina D1/metabolismo , Sunitinibe/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Simulação de Acoplamento Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Pâncreas/patologia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Piperazinas/química , Piperazinas/uso terapêutico , Receptores de Dopamina D1/química , Sunitinibe/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A food adhesive comprising tannic acid (TA) and soybean protein isolate (SPI) was developed to establish a cohesive bond between soy protein gel and simulated fat. The impact of varying TA concentrations and pH levels on the adhesive's rheology, thermal stability, chemical structure, and tensile strength were investigated. Rheological results revealed a gradual decrease in adhesive viscosity with increasing TA content. Differential scanning calorimetry (DSC) and thermal gravimetric (TG) results indicated that the stability of the adhesive improved with higher TA concentrations, reaching its peak at 0.50% TA addition. The incorporation of TA resulted in the cross-linking of amino group in unfolded SPI molecules, forming a mesh structure. However, under alkaline conditions (pH 9), adhesive viscosity and stability increased compared to the original pH. This shift was due to the disruption of the SPI colloidal charge structure, an increase in the stretching of functional groups, further unfolding of the structure, and an enhanced binding of SPI to TA. Under the initial pH conditions, SPI reacted with TA's active site to form covalent crosslinked networks and hydrogen bonds. In alkaline condition, beyond hydrogen and ionic bonding, the catechol structure was oxidized, forming an ortho-quinone that crosslinked SPI and created a denser structure. Tensile strength measurements and freeze-thaw experiments revealed that the adhesive exhibited maximum tensile strength and optimal adhesion with 0.75% TA at pH 9, providing the best overall performance. This study provides a new formulation and approach for developing plant-based meat analogues adhesives.
Assuntos
Polifenóis , Reologia , Proteínas de Soja , Taninos , Resistência à Tração , Taninos/química , Proteínas de Soja/química , Concentração de Íons de Hidrogênio , Viscosidade , Adesivos/química , Substitutos da CarneRESUMO
The study aimed to evaluate a food adhesive developed using tea polyphenols (TPs) with soybean protein isolate (SPI) to create a cohesive bond between soy protein gel and simulated fat. Upon the addition of 5.0 % TPs, significant increases in viscosity, thermal stability, and crystallinity were noted in adhesives, suggesting the formation of a cohesive network. Furthermore, TPs effectively enhanced adhesion strength, with the optimal addition being 5.0 %. This enhancement can be attributed to hydrogen bonding, hydrophobic and electrostatic interactions between TPs and SPI molecules. TPs induced a greater expansion of the protein structure, exposing numerous buried hydrophobic groups to a more hydrophilic and polar environment. However, excessive TPs were found to diminish adhesion strength. This can be attributed to enhanced reactions between TPs and SPI, where high molecular weight SPI-TPs cooperatively aggregate to form agglomerates that eventually precipitated, rendering the adhesive network inhomogeneous, less stable, and more prone to disruption.