Journal
MOLECULES
Volume 27, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/molecules27113486
Keywords
curcumin; resveratrol; hybrid molecules; colorectal cancer; cell death; apoptosis; molecular docking
Funding
- University of Antioquia
- ICETEX, through the Program Ecosistema Cientifico [58537]
- MINCIENCIAS
- MINEDUCACION
- MINCIT
Ask authors/readers for more resources
In this study, hybrids based on curcumin and resveratrol were synthesized and evaluated for their potential anticancer properties. The results showed that these hybrids can induce mitochondrial instability and apoptotic processes in colon cancer cells. Furthermore, some of these compounds exhibited cytostatic effects by causing cell cycle arrest. These curcumin resveratrol hybrids could be promising candidates for further investigation as chemopreventive agents, especially in cases with resistance to conventional chemotherapy.
Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available