Combined dual effect of modulation of human neutrophils' oxidative burst and inhibition of colon cancer cells proliferation by hydroxycinnamic acid derivatives. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Tavares-da-Silva, Elisiário J.; Varela, Carla L.; Pires, Ana S.; Encarnação, João C.; Abrantes, Ana M.; Botelho, Maria F.; Carvalho, Rui A.; Proença, Carina; Freitas, Marisa; Fernandes, Eduarda; Roleira, Fernanda M.F.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 16(2016)
• Page Start: 3556
• Page End: 3564
• Publication Date: 2016-08-15
• Subjects: Hydroxycinnamic acid derivatives -- Synthesis -- Human neutrophils -- Oxidative burst -- Colon cancer cells -- Antiproliferative; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.05.065
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Hydroxycinnamic acid derivatives inhibit neutrophils' oxidative burst. Hydroxycinnamic acid derivatives inhibit colon cancer cells proliferation. The presence of a catechol group is very important for both activities. The most active derivative acts as antioxidant and prooxidant. The most active derivative triggers mitochondrial dysfunction leading cells to apoptosis. Abstract: Colon cancer is one of the most incident cancers in the Western World. While both genetic and epigenetic factors may contribute to the development of colon cancer, it is known that chronic inflammation associated to excessive production of reactive oxygen and nitrogen species by phagocytes may ultimately initiate the multistep process of colon cancer development. Phenolic compounds, which reveal antioxidant and antiproliferative activities in colon cancer cells, can be a good approach to surpass this problem. In this work, hydroxycinnamic amides and the respective acid precursors were tested in vitro for their capacity to modulate human neutrophils' oxidative burst and simultaneously to inhibit growth of colon cancer cells. A phenolic amide derivative, caffeic acid hexylamide (CAHA) (4 ) was found to be the most active compound in both assays, inhibiting human neutrophils' oxidative burst, restraining the inflammatory process, inhibiting growth of colon cancer cells and triggering mitochondrial dysfunction that leads cancer cells to apoptosis. Altogether, these achievements can contribute to the understanding of the relationship between antioxidant and anticancer activities and based on the structure–activity relationships (SAR) established can be the starting point to find more effective phenolic compounds as anticancer agents.