Abstract
Lunasin is a bioactive peptide that was originally isolated from soybean and has since been shown to have a number of biological activities, including both cancer chemopreventive and therapeutic activities. Our recent focus has been on determining the range of cancer types that lunasin can affect and the mechanism of action against specific cancers. We recently found that lunasin has significant therapeutic activity against non-small cell lung cancer (NSCLC) both in vitro and in vivo. Mechanistic studies using lunasin-sensitive and lunasin-resistant NSCLC cell lines revealed the lunasin blocks cell proliferation by inhibiting cell cycle progression at the G1/S phase interface and that this inhibition was associated with reduced Akt signaling. In addition, we found that these effects were linked to the inhibition of integrin signaling through αv-containing integrins. Our results provide strong support for the hypothesis that direct effects on integrin signaling represent a major mode of action responsible for lunasin’s anticancer activity.
Highlights
Numerous studies over the years have found a strong linkage of high soy consumption with a number of health benefits, including lower rates of cancer
It was initially speculated that the RGD cell adhesion motif is involved in lunasin internalization into the cell, and that helix domain and poly-D tail is required for binding with core histone H3 and H4.5 Based on these hypotheses, the initial proposed mechanism for lunasin action was that lunasin competes with histone acetyltransferases by binding to deacetylated histones, resulting in an inhibition of histone acetylation and a concomitant down regulation of cell cycle-related protein expression and the activation of apoptosis
To further assess lunasin effects on integrin signaling and extend our functional studies, we examined the activation of key integrin signaling components that are known to regulate cell proliferation using Western blot analyses
Summary
Numerous studies over the years have found a strong linkage of high soy consumption with a number of health benefits, including lower rates of cancer. It was initially speculated that the RGD cell adhesion motif is involved in lunasin internalization into the cell, and that helix domain and poly-D tail is required for binding with core histone H3 and H4.5 Based on these hypotheses, the initial proposed mechanism for lunasin action was that lunasin competes with histone acetyltransferases by binding to deacetylated histones, resulting in an inhibition of histone acetylation and a concomitant down regulation of cell cycle-related protein expression and the activation of apoptosis. Based on these studies, my laboratory has focused on characterizing the effects of lunasin on lung cancer and elucidating its mechanism of action
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