1–9-NαC]-linusorb B2 and [1–9-NαC]-linusorb B3 isolated from flaxseed induce G1 cell cycle arrest on SGC-7901 cells by modulating the AKT/JNK signaling pathway

Abstract

Linoorbitides (LOBs) are a family of naturally-occurring cyclic peptides in flaxseed. Previously, we reported that two different structural LOBs, [1–9-NαC]-linusorb B2 and [1–9-NαC]-linusorb B3, induced apoptosis towards SGC-7901 cells through an intrinsic and/or extrinsic pathway. In the present study, we found that that the 2 LOBs could dose-dependently induce cell cycle arrest of SGC-7901 cells in the G1 phase, accompanied with the downregulation of CDK2, CDK4, cyclin D3, cyclin E as well as upregulation of p21WAF1/CIP1 and p27KIP1 analyzed by Western blot. However, [1–9-NαC]-linusorb B2 was more sensitive in suppressing AKT activation than [1–9-NαC]-linusorb B3. In addition, inhibitor of JNK (SP600125), neither p38 (SB203580) nor ERK (PB98095), promoted [1–9-NαC]-linusorb B2- or [1–9-NαC]-linusorb B3-induced G1 phase arrest. In conclusion, the disruption of both JNK and AKT played a pivotal role in [1–9-NαC]-linusorb B2-induced G1 phase arrest, but only JNK was involved in [1–9-NαC]-linusorb B3-induced G1 phase arrest.