title: Effects of Tyroserleutide on phosphatidylinositol 3'-kinase/AKT pathway in human hepatocellular carcinoma cell.
abstract: Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide with in vitro and in vivo anticancer effects on human hepatocellular carcinoma BEL-7402 cells. In this study, we studied the effects of YSL on PI3K/AKT in the BEL-7402 cells to explore its anti-tumor mechanism. Results showed that YSL could up-regulate the mRNA and protein expression of tumor suppressor PTEN and increase their activities, meanwhile inhibited the mRNA and protein expression of oncogene AKT and decreased the kinase activities of AKT and PDK1. The resuming balance effect of YSL between PTEN and AKT could prevent the transmission of tumor cell proliferation signals in the PI3K/AKT pathway. Inhibition of AKT would change the status of downstream effectors in the PI3K/AKT pathway: (1) inhibition of AKT up-regulated expression of cell cycle regulatory factors of downstream - P21 and P27 which repressed cell cycle and inhibited proliferation of tumor cells. (2) Inhibition of AKT decreased the phosphorylation level of MDM2, and then increased the protein level of P53 which would accelerate death proceeding of tumor cells. (3) Inactivation of AKT removed its inhibition effect on phosphorylation of Bad, which might decrease protein level of apoptosis inhibitor Bcl-2 and Bcl-XL, damaging mitochondria of tumor cells and inducing apoptosis.
authors.affiliation: Department of Immunology, Tianjin Medical University , Tianjin , China .
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Huiting
authors.initials: H
authors.lastname: Wei
authors.forename: Junqiang
authors.initials: J
authors.lastname: Lv
authors.forename: Xuchun
authors.initials: X
authors.lastname: Che
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009842:Oligopeptides; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D058539:Phosphatidylinositol 3-Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C484773:H-Tyr-Ser-Leu-OH