Alzheimer's disease (AD) is characterized by the accumulation of tau protein tangles and amyloid-β (Aβ) plaques in the central nervous system (CNS), leading to progressive neurodegeneration. Hence, th Show more
Alzheimer's disease (AD) is characterized by the accumulation of tau protein tangles and amyloid-β (Aβ) plaques in the central nervous system (CNS), leading to progressive neurodegeneration. Hence, the discovery of disease-modifying agents capable of delaying the progression is essential for effective management. Aminonaphthoquinone (ANQ) is an attractive pharmacophore with various biological effects. This study explores the neuroprotective potentials of ANQ derivatives (1-18) using in vitro models of AD pathology (i.e., Aβ Show less
Anoikis resistance is a critical feature involved in tumor progression and chemoresistance. Finding approaches to improve the effect of chemotherapy on anoikis-resistant cancer cells is therefore crit Show more
Anoikis resistance is a critical feature involved in tumor progression and chemoresistance. Finding approaches to improve the effect of chemotherapy on anoikis-resistant cancer cells is therefore critically important. In this study, we examined the effects of curcumin in anoikis-resistant cholangiocarcinoma (CCA) cells, including HuCCT1 and TFK-1 that were anchorage-independently cultured (AI-cells) using poly (2-hydroxyethyl methacrylate). The AI-CCA cells were treated with curcumin alone or in combination with anti-cancer agents and their responses to each treatment were determined by cell viability assay. Gene expression in AI-cells was determined by quantitative real-time PCR. The potential involvement of angiopoietin-like 4 (ANGPTL4) in anoikis resistance was examined by gene knockdown. It was found that AI-cells tended to resist anti-cancer agents tested, especially AI-HuCCT1, which significantly resisted gemcitabine and suberoylanilide hydroxamic acid (SAHA). Curcumin alone significantly inhibited viability and colony formation of AI-cells. Moreover, curcumin combination significantly enhanced the treatment effect of SAHA on AI-HuCCT1 and AI-TFK-1 cells. Gene expression analysis revealed that ANGPTL4 was markedly upregulated in AI-CCA cells and its knockdown tended to sensitize AI-cells to cell death and treatments. In addition, curcumin treatment decreased phosphorylated STAT3 and expression levels of Mcl-1, HDACs and ANGPTL4. Altogether, these findings reveal the beneficial property of curcumin to potentiate chemotherapeutic effects on anoikis-resistant CCA cells, which might suggest the potential use of curcumin for cancer treatment. Show less