title: Tangeretin sensitizes SGS1-deficient cells by inducing DNA damage.
abstract: Tangeretin, a polymethoxyflavone found in citrus peel, has been shown to have antiatherogenic, anti-inflammatory, and anticarcinogenic properties. However, the underlying target pathways are not fully characterized. We investigated the tangeretin sensitivity of yeast (Saccharomyces cerevisiae) mutants for DNA damage response or repair pathways. We found that tangeretin treatment significantly reduced (p < 0.05) survival rate, induced preferential G1 phase accumulation, and elevated the DNA double-strand break (DSB) signal γH2A in DNA repair-defective sgs1Δ cells, but had no obvious effects on wild-type cells or mutants of the DNA damage checkpoint (including tel1Δ, sml1Δ mec1Δ, sml1Δ mec1Δ tel1Δ, and rad9Δ mutants). Additionally, microarray data indicated that tangeretin treatment up-regulates genes involved in nutritional processing and down-regulates genes related to RNA processing in sgs1Δ mutants. These results suggest tangeretin may sensitize SGS1-deficient cells by increasing a marker of DNA damage and by inducing G1 arrest and possibly metabolic stress. Thus, tangeretin may be suitable for chemosensitization of cancer cells lacking DSB-repair ability.
authors.affiliation: Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Shin Yen
authors.initials: SY
authors.lastname: Chong
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Wu
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lo
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D047309:Flavones / Q000494:pharmacology*; D050296:Microbial Viability; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D047309:Flavones; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases; D045643:DNA Repair Enzymes; C059006:tangeretin