title: Genistein and beta-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells.
abstract: BACKGROUND
  The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear.
  
  
  OBJECTIVE
  We investigated the individual enhancing effect and its possible mechanisms of genistein, daidzein, beta-carotene, retinoic acid, and alpha-tocopherol on the cell-growth-inhibitory effect of TSA in a human lung carcinoma cell line, A549.
  
  
  METHODS
  A549 cells were incubated with TSA (50 ng/mL) alone or in combination with the various nutritional factors for various times, and cell growth was measured. IMR90 cells, human lung fibroblasts, were also incubated with TSA alone or in combination with genistein or beta-carotene to determine the selectivity of these treatments. In addition, we studied effects on the cell cycle, caspase-3 activity, and DNA damage (by comet assay) in A549 cells.
  
  
  RESULTS
  After treatment for 72 h, 10-microM genistein or beta-carotene significantly enhanced the growth-inhibitory effect of TSA in A549 cells. Daidzein, retinoic acid, and alpha-tocopherol at the same concentration had no significant effect. However, genistein and beta-carotene failed to enhance the cell-growth-arrest effect of TSA in IMR90 cells. Flow cytometric analysis showed that both genistein and beta-carotene significantly increased the TSA-induced apoptosis in A549 cells. Genistein significantly enhanced TSA-induced caspase-3 activity in A549 cells by 34% at 24 h, and the caspase-3 inhibitor partly inhibited the enhancing effect of genistein on TSA-induced apoptosis. beta-Carotene did not significantly affect TSA-induced caspase-3 activity. However, beta-carotene rather than genistein enhanced TSA-induced DNA damage.
  
  
  CONCLUSIONS
  Genistein and beta-carotene enhance the cell-growth-arrest effect of TSA on A549 cells. Genistein exerts its effect, at least partly, by increasing caspase-3 activity; whereas beta-carotene may enhance TSA-induced cell death mainly through a caspase-3-independent pathway.
authors.affiliation: Department of Beauty Science, Chienkao Technology University, Changhua, Taiwan, ROC.
authors.forename: Rong-Jen
authors.initials: RJ
authors.lastname: Shiau
authors.forename: Kai-Yong
authors.initials: KY
authors.lastname: Chen
authors.forename: Yu-Der
authors.initials: YD
authors.lastname: Wen
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Chuang
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Yeh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008168:Lung; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D019207:beta Carotene; C012589:trichostatin A; D019833:Genistein; D053148:Caspase 3