Matrine inhibits the activity of translation factor eIF4E through dephosphorylation of 4E-BP1 in gastric MKN45 cells.
Matrine, from Sophora flavescens, could remarkably inhibit tumor growth and induce apoptosis in various cancer cells in vitro. eIF4E and its inhibitor 4E-BP1 play key roles in regulating mRNA translation and cell proliferation. However, it remained elusive whether matrine inhibited cancer cells growth through attenuating the activity of 4E-BP1. In this study, we analyzed the effects of matrine on 4E-BP1 and eIF4E in gastric cancer MKN45 cells. Immunoblots showed that matrine inhibited the activity of eIF4E through dephosphorylation of 4E-BP1 in a dose- and time-dependent manner. We found that matrine inactivated Erk1/2, an upstream regulator of 4E-BP1 and eIF4E, and remarkably reduced the phosphorylation level of 4E-BP1 and eIF4E, whereas 4E-BP1 was little influenced by JNK, p38 or Akt/mTOR. Inactivation of PP2A obviously decreased the phosphorylation of 4E-BP1 in matrine-treated cells. These findings suggested that matrine inhibits the activity of eIF4E by dephosphorylating 4E-BP1, which partly counts for the growth inhibition in gastric MKN45 cells.
Jiang
Tiejun
T
Cancer Institute, Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.
Zhu
Yongliang
Y
Luo
Cong
C
Lu
Xiaoyong
X
Zhang
Wo
W
Qiu
Fuming
F
Huang
Jian
J
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D029909:Sophora; D013274:Stomach Neoplasms / Q000473:pathology; D000093842:Matrines