Timosaponin Aiii Disrupts Morphological Plasticity and Migration of Breast Adenocarcinoma Through Inhibition of Integrin Internalisation

Cell migration is a critical step in tumour invasion and metastasis. To acquire invasive properties, cancer cells use their surrounding environment through dynamic and bidirectional interactions and change their morphology and mode of migration. Thus, inhibition of morphological plasticity regulated by paracrine interactions may be a promising approach for anti-cancer therapy. In this study, we found that timosaponin AIII (TAIII), a steroidal saponin isolated from the roots of Anemarrhena asphodeloides, disrupted the morphological changes and migratory activity of breast adenocarcinoma cells promoted by paracrine interactions with mammary epithelium-derived cells. TAIII suppressed lamellipodia formation of MDA-MB-231 cells in response to exogenous stimuli from MCF10A cells, thereby inhibiting morphological changes and migration. TAIII also attenuated membrane spreading and induced contraction of HeLa cells, followed by expansion of intercellular gaps. Furthermore, we analysed the intracellular dynamics of TAIII labelled with a fluorescent dye and found that labelled TAIII was internalised in a manner dependent on dynamin. We also found that TAIII blocked internalisation of cell surface proteins including integrin b1. These results provide a novel aspect to understand how TAIII exerts pharmacological activities in suppression of cancer cell migration.