Comparative Proteomic Study of the Antiproliferative Activity of Frog Host-Defence Peptide Caerin 1.9 and Its Additive Effect with Caerin 1.1 on TC-1 Cells Transformed with HPV16 E6 and E7.

Guoying Ni,Yuejian Wang,Di Liang,Xiaosong Liu,Tianfang Wang,Kate Mounsey,Jianwei Yuan,Ming Q Wei,Shu Chen,Scott F Cummins,Shelley F Walton,Xuan Pan

doi:10.1155/2018/7382351

Abstract

Caerin is a family of peptides isolated from the glandular secretion of Australian tree frogs, the genus Litoria, and has been previously shown to have anticancer activity against several cancer cells. In this work, we used two host-defence peptides, caerin 1.1 and caerin 1.9, to investigate their ability to inhibit a murine derived TC-1 cell transformed with human papillomavirus 16 E6 and E7 growth in vitro. Caerin 1.9 inhibits TC-1 cell proliferation, although inhibition is more pronounced when applied in conjunction with caerin 1.1. To gain further insights into the antiproliferative mechanisms of caerin 1.9 and its additive effect with caerin 1.1, we used a proteomics strategy to quantitatively examine (i) the changes in the protein profiles of TC-1 cells and (ii) the excretory-secretory products of TC-1 cells following caerin peptides treatment. Caerin 1.9 treatment significantly altered the abundance of several immune-related proteins and related pathways, such as the Tec kinase and ILK signalling pathways, as well as the levels of proinflammatory cytokines and chemokines. In conclusion, caerin peptides inhibit TC-1 cell proliferation, associated with modification in signalling pathways that would change the tumour microenvironment which is normally immune suppressive.

Highlights

Cervical cancer is the third most diagnosed cancer in woman and is associated with high risk human papillomavirus (HPV) infection, especially HPV subtypes 16 and 18 [1]
Compared to P3, caerin 1.1 and caerin 1.9 significantly inhibited the proliferation of TC-1 cells at 15, 10, and 8 μg/mL, respectively
Caerin 1.9 inhibited the proliferation of TC-1 cells in vitro and had dose-dependent additive effects when using in combination with caerin 1.1

Summary

Introduction

Cervical cancer is the third most diagnosed cancer in woman and is associated with high risk human papillomavirus (HPV) infection, especially HPV subtypes 16 and 18 [1]. Targeted therapies are currently under intensive investigation. These therapies target tumour cells either directly or via interfering with the tumour microenvironment (TME) [2]. Therapeutic vaccines target tumour cells without harming normal tissues or organs. To date therapeutic vaccines have only shown efficacies in some but not all patients [3]. One of the key problems that limit the effectiveness of therapeutic vaccines is the immune suppressive TME, which may prevent the migration of tumour killing effector cells to the tumour sites or the killing of the tumour cells [3, 4]. Targeting the TME coupled with therapeutic vaccines may provide an effective way for better treatment of cancers

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