title: Inositol hexaphosphate suppresses growth and induces apoptosis in HT-29 colorectal cancer cells in culture: PI3K/Akt pathway as a potential target.
abstract: BACKGROUND
  Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate that is present in high amounts in almost all plants and mammalian cells. IP6 induces apoptosis in multiple types of cancer cells, including prostate cancer, breast cancer, skin tumor, liver cancer and colorectal cancer. However, little is known regarding the molecular mechanisms of its anticancer effects. Therefore, this study was conducted to investigate the activity of IP6 against human colorectal cancer cells (HT-29) and to determine whether the IP6 regulates apoptosis in HT-29 cells by inhibiting the PI3K/Akt signaling pathway.
  
  
  METHODS
  A human colorectal cancer cell line (HT-29) was used for the study. HT-29 cells were treated with 0, 50, 100, 200, and 400 μg/mL of IP6. The MTT colorimetric assay was used to observe the proliferation of HT-29 in vitro, and flow cytometry (FCM) was used to analyze the apoptosis of the HT-29 cells. The relative mRNA expression was determined by real-time PCR, and relative protein levels were analyzed by Western blot analysis.
  
  
  RESULTS
  The results of MTT showed that HT-29 cells underwent inhibition of proliferation after exposure to IP6 (100-400 μg/mL) for 12 and 48 h, and this inhibition clearly relied on time and dosage. IP6 induced apoptosis in HT-29 cells in a dose-dependent manner. The mRNA and protein expression of PI3K and Akt decreased in the groups treated with IP6, and IP6 inhibited the phosphorylation of Akt (pAkt), whereas increased the expression of its downstream effector, caspase-9.
  
  
  CONCLUSIONS
  Our results suggested that by targeting PI3K/Akt pathway, IP6 suppresses cell survival and proliferation, but induces death in HT-29 cells.
authors.affiliation: Department of Public Health, Qingdao University Medical College Qingdao 266021, Shangdong, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Public Health, Qingdao University Medical College Qingdao 266021, Shangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Public Health, Qingdao University Medical College Qingdao 266021, Shangdong, China.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Cui
authors.affiliation: School of Nursing, Qingdao University Medical College Qingdao 266021, Shangdong, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Public Health, Qingdao University Medical College Qingdao 266021, Shangdong, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010833:Phytic Acid / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010833:Phytic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: HT-29; Inositol hexaphosphate; PI3K/Akt pathway; apoptosis; human colorectal cancer cell