METHODS: K562 CML cells were treated with resveratrol, and their effects were analyzed through CCK-8 assay for cell viability, TUNEL assay for DNA fragmentation, and real-time PCR for gene expression. Key apoptotic genes (BCL-2, AIF, BAX) were assessed alongside survival-related genes (CASP3, PGC1α, Cyclin-D1, p53) to evaluate resveratrol's anti-proliferative and pro-apoptotic potential.
RESULT: Resveratrol exhibited a time-dependent reduction in K562 cell viability, with IC₅₀ values decreasing from 282.2 µM at 24 hours to 107.1 µM and 102.4 µM at 48 and 72 hours, respectively. Apoptotic activity, assessed via the TUNEL assay, revealed significant DNA fragmentation in 55 ± 5% of treated cells, while control cells showed no fragmentation. Gene expression analysis demonstrated upregulation of pro-apoptotic genes, including BCL-2, AIF (p < 0.05), BAX (p < 0.01), and VDAC1 (4.5-fold, p < 0.001). Conversely, genes linked to cell survival and metabolism, such as CASP3, PGC1α, NDUFA9, Cyclin-D1, and p53, were slightly downregulated (p < 0.05), highlighting resveratrol's dual role in promoting apoptosis and inhibiting cell survival.
CONCLUSION: These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.
MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.
KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.
SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.
METHODS: A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10mg/kg PS (PS10) and 50mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis.
RESULTS: All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium.
CONCLUSIONS: The underlying molecular mechanisms of PS in lung SCC should be further studied.