Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells.

Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy.

A highly efficient synthetic strategy for de novo NP encapsulation into metal-organic frameworks: enabling further modulated control of catalytic properties.

De novo encapsulation is a prevalent method to prepare composite materials where the structure-tunable metal nanoparticles (NPs) are holistically coated with metal-organic frameworks (MOFs). This method has been demonstrated to have promise in various fields but the extensive application of this approach is still challenging. This study proposed, for the first time, leveraging a specific surface-energy-dominated (SED) mechanism to achieve a highly efficient synthetic strategy for de novo NP encapsulation. The generality of this strategy is proved in applying to various MOFs, reaction conditions and the use of capping agents. By applying the strategy, Pd NPs with different morphologies are encapsulated in UiO-67, which is prone to self-assembly without coating, and an interesting enhancement is investigated in the selective semihydrogenation of alkynes on different Pd surfaces. These results demonstrate that the control of surface energy is a feasible method for efficient NP encapsulation which sheds light on the rational design of MOF-based composites for future applications.