The bioavailability of quercetin, a natural compound, is hindered by low solubility, limited absorption, and restricted systemic availability. Therefore, encapsulating it in biocompatible nanoparticles presents a promising solution. This study aimed to target prostate cancer stem cells (CSCs) overexpressing CD44+ receptors as well as cancer cells, employing quercetin-loaded hyaluronic acid-modified nanoliposomes (LP-Quer-HA). Synthesized via a green ethanol injection method, these nanoliposomes had an average diameter of 134 nm and an impressive loading efficiency of 96.9%. Human prostate cancer cells were treated with either 10 μM of free quercetin or the same concentration delivered by LP-Quer-HA for 72 hours. Free quercetin reduced androgen-resistant PC3 cell viability by 16%, while LP-Quer-HA significantly increased cell death to 60%. It induced apoptosis, upregulating cytochrome c, Bax, caspases 3 and 8, and downregulating survivin and Bcl-2 expression. Compared to free quercetin, LP-Quer-HA upregulated E-cadherin expression while inhibiting cell migration and reducing the expression of fibronectin, N-cadherin, and MMP9. Treatment of PC3 cell tumor spheroids with LP-Quer-HA decreased the number of CD44 cells and expression of CD44, Oct3/4 and Wnt.Moreover, LP-Quer-HA inhibited p-ERK expression while increasing p38/MAPK and NF-κB protein expression. In androgen-sensitive LNCaP cells, LP-Quer-HA efficacy was notable, reducing cell viability from 10% to 52% compared to free quercetin. Utilizing HA-modified nanoliposomes as a quercetin delivery system enhanced its potency at lower concentrations, reducing the CD44+ cell population and effectively impeding prostate cancer cell proliferation and migration. These findings underscore the potential of quercetin-loaded cationic nanoliposomes as a robust therapeutic approach.

BACKGROUND: Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. METHODS: Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. RESULTS: Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. CONCLUSIONS: Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed.
Apoptosis ; Blotting, Western ; Cause of Death ; Cell Cycle Checkpoints ; Cell Cycle ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Survival ; Cytochromes c ; G1 Phase ; Gene Expression ; Humans ; Male ; Passive Cutaneous Anaphylaxis ; Phosphorylation ; Prostate ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Wound Healing

OBJECTIVES: We explored whether wideband tympanometry (WBT) could be used as a screening test for superior semicircular canal dehiscence (SSCD), and obtained new WBT data (given that the test is not yet in common clinical use) on patients with SSCD. METHODS: We compared the WBT data of patients clinically and radiologically diagnosed with SSCD in our hospital between 2013 and 2018 to those of healthy volunteers. We compared the resonance frequency (RF), maximum absorbance frequency (MAF), and maximum absorbance ratio (MAR). The t-test was used for statistical analysis with the significance level set to P<0.05. In addition, we used receiver operating characteristic analysis to derive cutoff values for SSCD diagnosis in terms of sensitivity and specificity. RESULTS: Seventeen patients (four with bilateral and 13 with unilateral disease; 17 ears) diagnosed with SSCD and 27 healthy volunteers (47 ears) were included. The mean RFs of the SSCD patients and healthy subjects were 548.7 Hz (range, 243 to 853 Hz) and 935.1 Hz (range, 239 to 1,875 Hz), respectively (P<0.001). The mean MARs of the SSCD patients and healthy subjects were 89.4% (range, 62% to 100%) and 82.4% (range, 63% to 99%), respectively (P=0.005). The mean MAFs of the SSCD patients and healthy subjects were 1,706.3 Hz (range, 613 to 3,816 Hz) and 2,668 Hz (range, 876 to 4,387 Hz), respectively (P<0.001). In terms of SSCD diagnosis, a MAR above 86% afforded 81% sensitivity and 77% specificity; an RF below 728 Hz, 86% sensitivity and 81% specificity; and an MAF below 1,835 Hz, 79% sensitivity and 67% specificity. CONCLUSION: WBT may be a useful clinical screening test for SSCD. The RF and MAF were lower, and the MAR higher, in SSCD patients than in normal controls.
Acoustic Impedance Tests ; Diagnosis ; Healthy Volunteers ; Humans ; Mars ; Mass Screening ; ROC Curve ; Semicircular Canals ; Sensitivity and Specificity