title: The antioxidants, vitamin A and E but not vitamin C and melatonin enhance the proapoptotic effects of irinotecan in cancer cells in vitro.
abstract: Irinotecan is one of the camptothecin analog which has been shown to have a broad spectrum of antitumor activities against various malignancies. The aim of this study was to evaluate the effect of vitamin A, C, E and melatonin on proapoptotic activity of irinotecan in human cancer cells in vitro. We observed that irinotecan induced apoptosis in all types of analyzed cell lines when used as a single agent. Combination of selected antioxidants with various doses of irinotecan (7.5-60μM) resulted in significant increase in apoptotic cell death in A549 and HT29 cancer cell lines. The highest killing efficiency was observed after co-incubation of the cells with irinotecan and vitamin A (10μM), or vitamin E (25μM), respectively. The addition of vitamin C and melatonin to irinotecan treatment did not promote increase in killing of cancer cells. Our results indicate that some antioxidants can enhance the proapoptoic activity (properties) of irinotecan in human cancer cells in vitro. These findings may be supportive for the optimization of therapeutic efficacy of irinotecan treatment.
authors.affiliation: University of Lodz, Department of General Genetics, Molecular Biology and Biotechnology, Laboratory of Cytogenetics, Lodz, Poland. Electronic address: renkon@biol.uni.lodz.pl.
authors.forename: Renata
authors.initials: R
authors.lastname: Kontek
authors.affiliation: University of Lodz, Department of General Genetics, Molecular Biology and Biotechnology, Laboratory of Cytogenetics, Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Jakubczak
authors.affiliation: University of New Mexico Health Sciences Center, Department of Pediatrics, Division of Hematology and Oncology, Albuquerque, NM, USA.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Matlawska-Wasowska
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004396:Coloring Agents; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D000077146:Irinotecan; D008550:Melatonin / Q000494:pharmacology*; D009336:Necrosis; D014801:Vitamin A / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004396:Coloring Agents; D014801:Vitamin A; D014810:Vitamin E; D000077146:Irinotecan; D008550:Melatonin; D001205:Ascorbic Acid; D002166:Camptothecin
keywords: Antioxidants; Apoptosis; Flow cytometry; Irinotecan; TUNEL