防御素是阳离子宿主防御肽(HDP)家族的组成部分,先天免疫的关键组成部分。除了它们的抗菌和免疫调节活性,许多HDP对肿瘤细胞产生多方面的影响,特别是肿瘤细胞迁移的直接溶瘤和/或抑制。因此,HDP已被探索作为有前途的抗癌疗法。人β-防御素2(HBD-2)代表了人类HDP的重要成员,具有强大的病原体杀灭能力,伤口愈合,细胞因子诱导和白细胞化学吸引功能。然而,其抗癌作用在很大程度上仍然未知。最近,我们证明了HBD-2与磷脂酰肌醇-4,5-二磷酸(PI(4,5)P2)强烈结合,防御素诱导的细胞死亡的关键介质和细胞迁移过程中的教学信使。因此,在这项研究中,我们试图研究HBD-2对肿瘤细胞的裂解和抗迁移作用。使用各种细胞生物学分析和共聚焦显微镜,我们表明HBD-2通过急性溶解细胞死亡而不是凋亡杀死肿瘤细胞。此外,我们的数据表明,尽管报道了PI(4,5)P2相互作用,HBD-2不影响细胞骨架依赖性肿瘤细胞迁移。一起,我们的发现为防御素生物学提供了进一步的见解,并为未来基于防御素的药物开发提供了信息。
Defensins form an integral part of the cationic host defence peptide (HDP) family, a key component of innate immunity. Apart from their antimicrobial and immunomodulatory activities, many HDPs exert multifaceted effects on tumour cells, notably direct oncolysis and/or inhibition of tumour cell migration. Therefore, HDPs have been explored as promising anticancer therapeutics. Human β-defensin 2 (HBD-2) represents a prominent member of human HDPs, being well-characterised for its potent pathogen-killing, wound-healing, cytokine-inducing and leukocyte-chemoattracting functions. However, its anticancer effects remain largely unknown. Recently, we demonstrated that HBD-2 binds strongly to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a key mediator of defensin-induced cell death and an instructional messenger during cell migration. Hence, in this study, we sought to investigate the lytic and anti-migratory effects of HBD-2 on tumour cells. Using various cell biological assays and confocal microscopy, we showed that HBD-2 killed tumour cells via acute lytic cell death rather than apoptosis. In addition, our data suggested that, despite the reported PI(4,5)P2 interaction, HBD-2 does not affect cytoskeletal-dependent tumour cell migration. Together, our findings provide further insights into defensin biology and informs future defensin-based drug development.