title: Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.
abstract: Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.
authors: Department of Biochemistry and Cell Biology, University of Rzeszow, Zelwerowicza 4, 35-601 Rzeszow, Poland. Electronic address: alewinska@o2.pl.
authors: Anna
authors: A
authors: Lewinska
authors: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors: Paulina
authors: P
authors: Jarosz
authors: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors: Joanna
authors: J
authors: Czech
authors: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors: Iwona
authors: I
authors: Rzeszutek
authors: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093 Warsaw, Poland.
authors: Anna
authors: A
authors: Bielak-Zmijewska
authors: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093 Warsaw, Poland.
authors: Wioleta
authors: W
authors: Grabowska
authors: Department of Genetics, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors: Maciej
authors: M
authors: Wnuk
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002211:Capsaicin
keywords: Cancer cells; Capsaicin; DNA damage; DNA methylation; Micronuclei; Oxidative stress