title: Impact of antioxidants on the ability of phenolic phytochemicals to kill HCT116 colon cancer cells.
abstract: Certain phenolic phytochemicals can kill cancer cells. Possible interference from antioxidants is a concern, and this issue has not been studied appreciably. Therefore, the effect of ascorbate and N-acetylcysteine on the ability of epigallocatechin gallate (EGCG) and curcumin to kill HCT116 colon cancer cells was examined. EGCG and curcumin each caused DNA damage in the cells. The DNA-damaging ability of EGCG, but not curcumin, was hindered by either ascorbate or NAC, which was also shown in HT29 and SW480 colon cancer cells. Also, iron chelators (deferoxamine and 2,2'-dipyridyl) inhibited the ability of EGCG, but not curcumin, to cause damage to the DNA in HCT116 cells. Interestingly, curcumin, but not EGCG, increased the expression of growth arrest and DNA damage-inducible gene 153 and also heme oxygenase-1, and this stress gene upregulation by curcumin was antioxidant-insensitive. With prolonged incubation of HCT116 cells with either EGCG or curcumin, cell shrinkage, membrane blebbing, apoptotic bodies, and chromatin condensation/fragmentation were observed. These morphological changes were not apparent in EGCG-treated cells that had been pretreated with either ascorbate or NAC. However, the ascorbate and NAC pretreatments did not prevent the occurrence of the morphological changes in curcumin-treated cells. Thus, these findings suggest that ascorbate and NAC interfere with the ability of EGCG, but not curcumin, to kill HCT116 cells. This basic knowledge may help to better plan and optimize strategies for chemoprevention or chemotherapy.
authors.affiliation: Department of Nutrition, Cellular and Molecular Nutrition Research Laboratory, University of North Carolina at Greensboro , Greensboro, NC , USA.
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.forename: K
authors.initials: K
authors.lastname: Testa
authors.forename: J
authors.initials: J
authors.lastname: Berkelhammer
authors.forename: S
authors.initials: S
authors.lastname: Hopkins
authors.forename: G
authors.initials: G
authors.lastname: Loo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D007502:Iron Chelating Agents; D002392:Catechin; D051547:Heme Oxygenase-1; C057580:gallocatechol; D003474:Curcumin; D001205:Ascorbic Acid; D000111:Acetylcysteine