Chalcone Derivatives Suppress Proliferation and Migration of Castration-resistant Prostate Cancer Cells Through FAK-mediated DNA Damage.

BACKGROUND/AIM: Castration-resistant prostate cancer (CRPC) contributes to the deaths of most men from prostate cancer. Focal adhesion kinase (FAK) is abnormally up-regulated in CRPC. Chalcone possesses potent anticancer activity with clinical potential. However, it remains unknown whether its derivatives can be exploited as promising oncotherapeutic agents in CRPC treatment by inhibiting FAK-related signaling pathway. AIM: This study aimed to investigate the anticancer effects and the underlying mechanisms of action of chalcone derivatives against CRPC cells. MATERIALS AND METHODS: Two chalcone derivatives (compounds 1 and 2) were synthesized, and their anti-CRPC activity toward DU145 and PC3 cells was evaluated. The effect of chalcone derivatives on CRPC cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, 5-ethynyl-2'-deoxyuridine staining, flow cytometric, cell adhesion and transwell assays. The study of mechanisms was conducted through comet, immunofluorescence and western blot assay, analysis of The Cancer Genome Atlas and molecular docking. RESULTS: The results revealed that both compounds exhibited stronger cytotoxicity to CRPC cells along with significant inhibition of colony formation, especially compound 1 Further experimental evidence indicated that 1 significantly inhibited DNA replication, induced cell-cycle arrest and cell apoptosis. Additionally, treatment with 1 inhibited cell-matrix adhesion and migration of CRPC cells. Mechanistically, the results suggest that 1 inhibited FAK expression and phosphorylation, as well as affected its distribution, resulting in intense DNA damage and strong DNA damage response. CONCLUSION: We discovered two chalcone derivatives and collective results indicated that 1 inhibited CRPC cell proliferation and migration through FAK-mediated DNA damage and may be a potential therapeutic drug against CRPC.

Impact of internet plus health education on urinary stoma caregivers in coping with care burden and stress in the era of COVID-19.

Objective: To explore the impact of "Internet Plus Health Education" on coping with care burden and pressure in urinary stoma caregivers in the era of COVID-19. Materials and methods: Eighty caregivers of patients with urinary ostomy were equally randomized to experimental and control groups. Caregivers in the experimental group received digital nursing education intervention, which involved nursing intervention of Internet Plus Health Education (IPHE), and those in the control group received conventional care instructions. Six months later, care burden and emotional pressure were assessed in all caregivers using the Zarit Caregiver Burden Interview (ZBI) and the Simplified Coping Style Questionnaire (SCSQ). Results: Before the intervention, the ZBI and SCSQ scores were comparable between both groups (p > 0.05). After the intervention, the ZBI scores in the experimental group were significantly higher than in the control group and vice versa for SCSQ scores (p < 0.01). Furthermore, after the intervention, the family care satisfaction scale (FCSS) of the experimental group was significantly higher than the control group. Conclusion: Providing "Internet Plus Health Education" to urinary stoma caregivers can reduce their care burden and enhance their pressure-coping ability in the COVID-19 era.