Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Davis, Keith R.
Committee Co-Chair (if applicable)
States, J. Christopher
Ceresa, Brian P.
Clark, Geoffrey J.
Peptides--Physiological effect; Cancer--Treatment
Lunasin is a 44 amino acid peptide derived from the soybean seed that has been shown to have cancer chemopreventive and chemotherapeutic properties. In this study, we investigated the potential utility of lunasin as a chemotherapeutic in a melanoma model. Initial studies showed that lunasin has little activity against established melanoma cell lines in vitro using adherent culture methods; however, lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays in soft agar and oncosphere assays. These results led us to investigate whether lunasin selectively affects cancer initiating cells (CIC) that are known to be present in these melanoma cell lines. We found that lunasin treatment did selectively inhibit the proliferation of high-ALDH-expressing malignant melanoma initiating cells (MMIC) in vitro, and had the striking effect of preventing oncosphere formation under non-adherent culture conditions. These in vitro results were extended into mouse xenograft studies using both bulk melanoma cells and isolated CICs. Lunasin significantly inhibited tumor growth in both cases, with the highest inhibition being observed in tumors initiated by MMICs. Mechanistic studies suggested that lunasin inhibits CIC proliferation in vitro through interactions with integrins and disruption of integrin signaling by inhibiting the activity of integrin binding partners such as integrin-linked kinase (ILK) and focal adhesion kinase (FAK). These studies demonstrate for the first time that lunasin has activity against putative CICs and that lunasin may have utility as a therapeutic agent for the treatment of melanoma.
Shidal, Christopher Paul, "Lunasin reduces the melanoma stem cell population in vitro and inhibits tumor proliferation in vivo." (2014). Electronic Theses and Dissertations. Paper 1765.