School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide & Protein Science, The University of Sydney, Sydney, NSW, Australia.
Sci Rep. 2023 Aug 4;13(1):12698. doi: 10.1038/s41598-023-39901-0.
The Tasmanian devil (Sarcophilus harrisii) is endangered due to the spread of Devil Facial Tumour Disease (DFTD), a contagious cancer with no current treatment options. Here we test whether seven recently characterized Tasmanian devil cathelicidins are involved in cancer regulation. We measured DFTD cell viability in vitro following incubation with each of the seven peptides and describe the effect of each on gene expression in treated cells. Four cathelicidins (Saha-CATH3, 4, 5 and 6) were toxic to DFTD cells and caused general signs of cellular stress. The most toxic peptide (Saha-CATH5) also suppressed the ERBB and YAP1/TAZ signaling pathways, both of which have been identified as important drivers of cancer proliferation. Three cathelicidins induced inflammatory pathways in DFTD cells that may potentially recruit immune cells in vivo. This study suggests that devil cathelicidins have some anti-cancer and inflammatory functions and should be explored further to determine whether they have potential as treatment leads.
塔斯马尼亚恶魔（Sarcophilus harrisii）由于恶魔面部肿瘤疾病（DFTD）的传播而濒临灭绝，这种传染性癌症目前尚无治疗方法。在这里，我们测试了七种最近描述的塔斯马尼亚恶魔 cathelicidins 是否参与癌症调控。我们在体外用七种肽之一孵育 DFTD 细胞后测量其活力，并描述每种肽对处理细胞中基因表达的影响。四种 cathelicidins（Saha-CATH3、4、5 和 6）对 DFTD 细胞有毒，并导致一般的细胞应激迹象。最毒的肽（Saha-CATH5）还抑制了 ERBB 和 YAP1/TAZ 信号通路，这两个通路都被认为是癌症增殖的重要驱动因素。三种 cathelicidins 在 DFTD 细胞中诱导炎症通路，这些通路可能在体内招募免疫细胞。这项研究表明，恶魔 cathelicidins 具有一些抗癌和抗炎功能，应进一步探索，以确定它们是否具有作为治疗方法的潜力。
