The soy-derived peptide Lunasin inhibits invasive potential of melanoma initiating cells

Abstract

Lunasin is a 44 amino acid peptide with multiple functional domains including an aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We recently showed that Lunasin induced a phenotype switch of cancer initiating cells (CIC) out of the stem compartment by inducing melanocyte-associated differentiation markers while simultaneously reducing stem-cell-associated transcription factors. In the present study, we advance the hypothesis that Lunasin can reduce pools of melanoma cells with stem cell-like properties, and demonstrate that Lunasin treatment effectively inhibits the invasive potential of CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice receiving Lunasin treatment had significantly reduced pulmonary colonization after injection of highly metastatic B16-F10 melanoma cells compared to mice in the control group. Mechanistic studies demonstrate that Lunasin reduced activating phosphorylations of the intracellular kinases FAK and AKT as well as reduced histone acetylation of lysine residues in H3 and H4 histones. Using peptides with mutated activity domains, we functionally demonstrated that the RGD domain is necessary for Lunasin uptake and its ability to inhibit oncosphere formation by CICs, thus confirming that Lunasin's ability to affect CICs is at least in part due to the suppression of integrin signaling. Our studies suggest that Lunasin represents a unique anticancer agent that could be developed to help prevent metastasis and patient relapse by reducing the activity of CICs which are known to be resistant to current chemotherapies.

Oral Administration of CardioAid and Lunasin Alleviates Liver Damage in a High-Fat Diet Nonalcoholic Steatohepatitis Model

“…Its chemical structure was previously described [19]. Lunasin was extensively studied for various indications [5,6,9,20,21,22,23,24,25,26,27,28]. …”

Updating the research on the chemopreventive and therapeutic role of the peptide lunasin

“…Moreover, the mechanistic model revealed that lunasin, added to isolated melanoma cancer‐initiating cells, induced expression of the melanocyte‐associated differentiation markers tyrosinase and microphthalmia‐associated transcription factor concomitant with reduced expression of the stem‐cell‐associated marker NANOG. A subsequent study of these authors demonstrated robust antimetastatic properties of lunasin through alterating histone acetylation patterns and modulating integrin signalling through FAK and PI3K/AKT pathways . Lunasin is shown as a complex and multifaceted peptide with potential therapeutic efficacy against malignant diseases in which recurrence resulting from cancer‐initiating cells is expected.…”

“…In a melanoma xenograft mouse model, it has been shown that the in vivo tumour growth initiated by the cancer‐initiating cells population was significantly impaired by treatment with lunasin . Also, when C57Bl/6 mice were subjected to an experimental metastasis model of melanoma using B16‐F10 cells, lunasin significantly suppressed the ability of these cells to invade and proliferate in the lungs . Since several mice in the lunasin‐treated group did not display any macrometastasis sign, the authors suggested the efficacy of lunasin to reduce or abolish metastatic burden.…”

“…A subsequent study of these authors demonstrated robust antimetastatic properties of lunasin through alterating histone acetylation patterns and modulating integrin signalling through FAK and PI3K/AKT pathways. 75 Lunasin is shown as a complex and multifaceted peptide with potential therapeutic efficacy against malignant diseases in which recurrence resulting from cancer-initiating cells is expected.…”

“…74 Also, when C57Bl/6 mice were subjected to an experimental metastasis model of melanoma using B16-F10 cells, lunasin significantly suppressed the ability of these cells to invade and proliferate in the lungs. 75 Since several mice in the lunasin-treated group did not display any macrometastasis sign, the authors suggested the efficacy of lunasin to reduce or abolish metastatic burden. The lunasin's ability to inhibit subcutaneous tumour growth of murine models of melanoma and non-small cell lung cancer has been also demonstrated.…”