Validation of syngeneic mouse models of melanoma and non-small cell lung cancer for investigating the anticancer effects of the soy-derived peptide Lunasin.

Bharat Devapatla,Kavitha Yaddanapudi,Chris Shidal,Keith R Davis

doi:10.12688/f1000research.9661.1

Bharat Devapatla, Kavitha Yaddanapudi + Show 2 more

Open Access

https://doi.org/10.12688/f1000research.9661.1

Copy DOI

Abstract

Background : Lunasin is a naturally occurring peptide present in soybean that has both chemopreventive and therapeutic activities that can prevent cellular transformation and inhibit the growth of several human cancer types. Recent studies indicate that Lunasin has several distinct potential modes of action including suppressing integrin signaling and epigenetic effects driven by modulation of histone acetylation. In addition to direct effects on cancer cells, Lunasin also has effects on innate immunity that may contribute to its ability to inhibit tumor growth in vivo. Methods: Standard assays for cell proliferation and colony formation were used to assess Lunasin's in vitro activity against murine Lewis lung carcinoma (LLC) and B16-F0 melanoma cells. Lunasin's in vivo activity was assessed by comparing the growth of tumors initiated by subcutaneous implantation of LLC or B16-F0 cells in Lunasin-treated and untreated C57BL/6 mice. Results: Lunasin was found to inhibit growth of murine LLC cells and murine B16-F0 melanoma cells in vitro and in wild-type C57BL/6 mice. The effects of Lunasin in these two mouse models were very similar to those previously observed in studies of human non-small cell lung cancer and melanoma cell lines. Conclusions: We have now validated two established syngeneic mouse models as being responsive to Lunasin treatment. The validation of these two in vivo syngeneic models will allow detailed studies on the combined therapeutic and immune effects of Lunasin in a fully immunocompetent mouse model.

Highlights

Lunasin is a multifunctional bioactive peptide present as a component of the storage protein fraction in soybean seeds and in soy-derived food products[1–4]
Mice were randomly placed into groups (6–10 mice per group) and received subcutaneous injections of Lewis lung carcinoma (LLC) (1 × 105) or B16-F0 (1 × 106) cells suspended in 100 μL of phosphate buffered saline (PBS) in the hind flank
The difference in activity observed in adherent versus non-adherent assays recapitulates our previous results using human nonsmall cell lung cancer (NSCLC) and melanoma cells and likely reflects differences in integrin expression profiles under these distinct culture conditions[8,15]

Summary

Introduction

Lunasin is a multifunctional bioactive peptide present as a component of the storage protein fraction in soybean seeds and in soy-derived food products[1–4]. Given that Lunasin has both direct therapeutic effects on cancer cells as well as the ability to affect immunity, we were prompted to determine if syngeneic mouse cancer models could be identified where both of these activities could be studied in concert so that the relative contribution of these two different effects on the potent in vivo activity of Lunasin could be determined. In these studies, we demonstrate that Lunasin has significant in vitro and in vivo activity in syngeneic mouse models for lung cancer and melanoma. These syngeneic models will provide the ability to pursue studies of Lunasin action in an immunocompetent host and use genetic approaches to understand how specific genetic manipulations affect Lunasin’s ability to inhibit tumor growth and metastasis

Methods

Results and discussion

Conclusion

Are the concentrations of Lunasin used physiologically relevant?