4’-bromo-Resveratrol is a potent inhibitor of the deacetylases sirtuin 1 (SIRT1) and 3 (SIRT3). It is a brominated derivative of resveratrol, a polyphenol found in red wine, which activates SIRT1 and inhibits SIRT3. The use of 4’-bromo-resveratrol in an SIRT3 crystal binding study revealed two compound binding sites which, combined with homology modeling, suggested that the second site may account for the paradoxical activation of SIRT1 by unmodified resveratrol.
4'-Bromo-resveratrol is a dual SIRT1/SIRT3 inhibitor with an IC50 of 0.2 mM for both targets. 4'-Bromo-resveratrol induces caspase-dependent apoptosis, induces G0/G1 cell cycle arrest, and inhiibits proliferation. 4'-Bromo-resveratrol reduces lactate production, glucose uptake, and NAD+/NADH ratio, and downregulates lactate dehydrogenase A and glucose transporter 1 (GLUT1). 4'-Bromo-resveratrol can be used for the research of melanoma.
IC50&Target
SIRT1 SIRT3 Caspase 3 Caspase 8 GLUT1 LDHA
0.2 mM (IC50) 0.2 mM (IC50)
体外研究
4 '- Bromo resveratrol (0.0125-0.2 mM; 24-72 h) can dose - and time-dependent inhibit the proliferation and survival of G361, SK-MEL-28, and SK-MEL-2 human melanoma cells.
4 '- Bromo resperatrol (0.0125-0.2 mM; 48 h) can dose dependently damage the clonal survival ability of G361, SK-MEL-28, and SK-MEL-2 human melanoma cells.
4 '- Bromo resveratrol (0.0125-0.05 mM; 24-72 h) can induce apoptosis in G361, SK-MEL-28, and SK-MEL-2 human tumor cells in a dose - and time-dependent manner, resulting in morphological changes of apoptosis, including nuclear condensation and fragmentation.
4 '- Bromo resparatrol (0.05 mM; 48 h) was used to induce Cyclin D1 and CDK6 inhibition through P21, mediating G0/G1 phase arrest in G361, SK-MEL-28, and SK-MEL-2 human melanoma cells.
4 '- Bromo resveratrol (0.05 mM; 48 h) can reduce the expression of glycolysis related proteins LDHA and GLUT1 in G361, SK-MEL-28, and SK-MEL-2 human melanoma cells.
4 '- Bromo resveratrol (0.05 mM; 48 h) significantly inhibited the migration of G361, SK-MEL-28, and SK-MEL-2 human melanoma cells.
4 '- Bromo resveratrol (0.025-0.05 mM; 48 h) can dose dependently inhibit aerobic glycolysis in G361, SK-MEL-28, and SK-MEL-2 human melanoma cells, reducing lactate production, glucose uptake, and NAD+/NADH ratio.
Cell Proliferation Assay
Cell Line:
G361, SK-MEL-28, SK-MEL-2 cells
Concentration:
0.0125, 0.025, 0.05, 0.1, 0.2 mM
Incubation Time:
24,48,72 hours
Result:
Inhibited melanoma cell proliferation and viability in a dose- and time-dependent manner. Caused massive reduction in proliferation at 0.1 mM and 0.2 mM. Induced appreciable growth inhibition at 0.025 mM, with statistically significant differences compared to vehicle control.
Apoptosis Analysis
Cell Line:
G361, SK-MEL-28, SK-MEL-2
Concentration:
0.0125, 0.025, 0.05 mM
Incubation Time:
24,48,72 hours
Result:
Increased the percentage of apoptotic cells across all three melanoma cell lines in a doseand time-dependent manner. Showed statistically significant differences compared to vehicle control.
Cell Cycle Analysis
Cell Line:
G361, SK-MEL-28, SK-MEL-2
Concentration:
0.05 mM
Incubation Time:
48 hours
Result:
Caused a significant increase in the percentage of cells in the G0/G1 phase across all three melanoma cell lines. Induced a concomitant decrease in the G2/M phase population across all three melanoma cell lines. Showed statistically significant differences compared to vehicle control.
Western Blot Analysis
Cell Line:
G361, SK-MEL-28, SK-MEL-2
Concentration:
0.05 mM
Incubation Time:
48 hours
Result:
Decreased protein levels of procaspase-3 and procaspase-8. Increased levels of cleaved caspase-3. Induced cleavage of full-length PARP (116 kDa) to its 89 kDa cleaved product. Significantly diminished expression of PCNA across all three melanoma cell lines.\nAttenuated protein levels of Cyclin D1 and CDK6 across all three melanoma cell lines. Induced expression of the CDK inhibitor P21 across all three melanoma cell lines.\nSignificantly decreased protein levels of lactate dehydrogenase A (LDHA) across all three melanoma cell lines. Reduced expression of glucose transporter 1 (GLUT1) across all three melanoma cell lines.