Host-defence peptides caerin 1.1 and 1.9 stimulate TNF-alpha-dependent apoptosis in human cervical cancer HeLa cells

ABSTRACT: TNFα pathway has been recognised as one of the most important signalling pathways characterising molecules with anti-cancer activity, due to it closely relates to cell survival as well as apoptosis. Isolated from the glandular secretion of Australian tree frogs, the genus Litoria, host-defence caerin peptides have been previously shown to have multiple biological activities, including anti-proliferation of several cancer cell lines, though the mechanism remains unclear. In this study, we used multiple immunoassays, confocal microscopy in conjunction with TMT-labelling quantitative proteomics to investigate the anti-proliferative activities of caerin 1.1 and 1.9 against cervical cancer HeLa cells. The proteins of cells and cell growth environment post the treatments were comparatively analysed, respectively. We found that both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect. The PPI analysis confirmed that the interactions among the significantly regulated proteins were highly intensive. Besides translation, folding and localisation of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptosis process was resulted by TNFα signalling, confirmed by the elevated levels of CASP3 and CASP9. Moreover, EGFR1 and androgen receptor pathways appeared inhibited. The activation of TCR pathway derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of Hela cells.

INSTRUMENT(S): X500R QTOF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Hela Cell

DISEASE(S): Breast Cancer

SUBMITTER: Tianfang Wang  

LAB HEAD: Tianfang Wang

PROVIDER: PXD015975 | Pride | 2020-08-27

REPOSITORIES: Pride