title: Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells.
abstract: OBJECTIVE
  To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells.
  
  
  METHODS
  PTEN-deficient colorectal cancer (CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin, 5-fluorouracil (5-FU), dihydroartemisinin (DHA), irinotecan (CPT-11) and oxaliplatin (OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed, and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry. Levels of apoptosis and cell cycle-related proteins were examined by Western blotting.
  
  
  RESULTS
  We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines, we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to 5-FU, CPT-11, DHA, or OXA, whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However, PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest. In HCT116 PTEN (+/+) cells, curcumin caused a G2/M phase arrest, whereas it caused a G0/G1 phase arrest in HCT116 PTEN (-/-) cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest.
  
  
  CONCLUSIONS
  Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells, suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.
authors.affiliation: Lin Chen, Hong-Xiao Wang, Hai-Na Zhao, Jia-Jia Tang, Chang-Jie Wu, Li-Ting Lu, Wan-Qin Liao, Xin-Cheng Lu, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.forename: Hong-Xiao
authors.initials: HX
authors.lastname: Wang
authors.forename: Hai-Na
authors.initials: HN
authors.lastname: Zhao
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Tang
authors.forename: Chang-Jie
authors.initials: CJ
authors.lastname: Wu
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Lu
authors.forename: Wan-Qin
authors.initials: WQ
authors.lastname: Liao
authors.forename: Xin-Cheng
authors.initials: XC
authors.lastname: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D003474:Curcumin
keywords: AKT signaling; Cell cycle; Chemotherapeutic agents; Curcumin; Phosphatase and tensin homolog deleted on chromosome 10