title: Quercetin Enhances Chemosensitivity to Gemcitabine in Lung Cancer Cells by Inhibiting Heat Shock Protein 70 Expression.
abstract: Quercetin is a bioflavonoid known for antioxidation and antiproliferation activities. We demonstrated that quercetin inhibited cancer cell growth and sensitized cancer cells to gemcitabine treatment by promoting apoptosis via inhibiting heat shock protein 70 expression. Our results suggest that quercetin might have potential to increase sensitivity to chemotherapy and that heat shock protein 70 could be a new target for lung cancer treatment.
  
  
  BACKGROUND
  Quercetin is a bioflavonoid with antiproliferative and proapoptotic activity in various cancer cells. However, little is known about the mechanism by which quercetin inhibits cancer growth or its potential role as a chemosensitizer in lung cancer cells. We investigated whether quercetin-induced inhibition of heat shock protein 70 (HSP70) is involved in its anticancer activity and whether it could modulate the responsiveness of lung cancer cells to chemotherapy.
  
  
  METHODS
  Various concentrations of quercetin and gemcitabine, either alone or in combination, were applied to lung cancer cells (A549 and H460 cells). We evaluated cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt assay, apoptotic activity by determining caspase-3 and caspase-9 activities, and HSP70 expression using Western blot analysis after treatment.
  
  
  RESULTS
  Quercetin reduced cell viability and suppressed HSP70 expression in both cell lines dose-dependently. Adding a fixed quercetin dose enhanced gemcitabine-induced cell death, which was related to increased caspase-3 and caspase-9 activities. Combination treatment with quercetin and gemcitabine downregulated HSP70 expression more prominently than treatment with quercetin or gemcitabine alone.
  
  
  CONCLUSIONS
  Quercetin-induced HSP70 inhibition was involved in growth inhibition and sensitization to chemotreatment in lung cancer cells. Quercetin might have potential as a chemosensitizer in lung cancer treatment.
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, KEPCO Medical Center, Seoul, Republic of Korea.
authors.forename: Seung Hyeun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: pulsy@korea.ac.kr.
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D000093542:Gemcitabine
chemical_list: D054316:Biomarkers, Pharmacological; D018840:HSP70 Heat-Shock Proteins; D003841:Deoxycytidine; D011794:Quercetin; D020169:Caspases; D000093542:Gemcitabine
keywords: Apoptosis; Gemcitabine; Heat shock protein; Lung cancer; Quercetin