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The aim of this study was to investigate the cellular uptake and antitumor activity of 2 different structural flaxseed orbitides ([1–9-NαC]-linusorb B2 containing methionine residue and [1–9-NαC]-linusorb B3 containing isoleucine residue) in SGC-7901 cells as well as its underlying molecule mechanism. Results showed that the absorption efficiency of [1–9-NαC]-linusorb B3 was higher than that of [1–9-NαC]-linusorb B2. Besides, through the evaluation of mitochondrial membrane potential (Δφm), cytochrome c (Cyt C) release, caspase, death receptor activation and cleavage of PARP, we found that [1–9-NαC]-linusorb B3 exhibited more obvious apoptosis induction on SGC-7901 cells than [1–9-NαC]-linusorb B2. Interestingly, [1–9-NαC]-linusorb B3-induced cell apoptosis might involve a mitochondrial- and death receptor-mediated intrinsic and extrinsic pathway; however, [1–9-NαC]-linusorb B2 induced cell apoptosis by the activation of Fas, FasL, caspase 8 as well as caspase 3 instead of Bax, Cyt C, tBid and caspase 9, suggesting that extrinsic pathway might be involved in the apoptotic process.