Biological Activity
Resveratrol is a phenolic phytoalexin found in grape skin and at least 72 other plant species that is involved in a diverse range of biological activities (and targets) with anti-inflammatory, cardiovascular protective, cancer chemopreventive, among other beneficial properties. [1,2] It was also found to increase CRISPR-mediated HDR efficiency, but more research is needed to understand its underlying mechanism. [3]
| Target Enzyme - list not inclusive (in vitro) | ED50[ 4 ] | IC50[ 4 ] |
| COX-1 (cyclooxygenase inhibition) | 15[5] | 15[6] |
| COX-1 (hydroperoxidase inhibition) | 3.7[5] | 3.7[6] |
| ERK1 | 37[2] | |
| JNK1 | 50[2] | |
| Src | 20[2] | |
| PKCα | < 10[2] | |
| Aromatase/CYP19 | 25[2] | |
| DNA polymerase α | 3.3 [2] | |
| DNA polymerase δ | 5[2] |
Successful Applications in CRISPR
(i) Li and colleagues found that resveratrol increased the expression of several CRISPR/Cas9-mediated HDR associated genes including RAD51 in porcine fetal fibroblasts. Results from an eGFP reporter assay demonstrated that HDR efficiency was increased by approximately 3-fold. Maximal effects were achieved with 50 μM of resveratrol. [3] * The authors note that resveratrol demonstrated cytotoxic action in a dosage-dependent manner and that it could arrest cells at the S phase. (ii) The effect of resveratrol on HDR-mediated (large fragment) knock-in was also examined in primary porcine
Reference:
- Szewczuk, L. M., Forti, L., Stivala, L. A., & Penning, T. M. (2004). Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. The Journal of biological chemistry, 279(21), 22727–22737. https://doi.org/10.1074/jbc.M314302200
- Pirola, L., & Fröjdö, S. (2008). Resveratrol: one molecule, many targets. IUBMB life, 60(5), 323–332. https://doi.org/10.1002/iub.47
- Li, G., Zhang, X., Zhong, C., Mo, J., Quan, R., Yang, J., Liu, D., Li, Z., Yang, H., & Wu, Z. (2017). Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Scientific reports, 7(1), 8943. https://doi.org/10.1038/s41598-017-09306-x
- Linardic, C. M., Jayadev, S., & Hannun, Y. A. (1996). Activation of the sphingomyelin cycle by brefeldin A: effects of brefeldin A on differentiation and implications for a role for ceramide in regulation of protein trafficking. Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research, 7(6), 765–774.
- Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., Fong, H. H., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., Moon, R. C., & Pezzuto, J. M. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science (New York, N.Y.), 275(5297), 218–220. https://doi.org/10.1126/science.275.5297.218
- Maccarrone, M., Lorenzon, T., Guerrieri, P., Agro, A. F. (1999). Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity. European Journal of Biochemisty, 265(1), 27-34. https://doi.org/10.1046/j.1432-1327.1999.00630.x
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