Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation

Abstract

AbstractBackgroundBreast cancer (BC) can be divided into five subtypes: Lumina1A, Lumina1B, HER-2 overexpression, Basal-like and Normal breast-like subtype, based on the differently expressed genes in breast cancer tissue. The Hippo signaling pathway plays an indispensable role in BC. The YAP gene is a terminal effector of Hippo pathway, and hyperactivation of YAP mediates tumorigenesis. As an inhibitor of YAP, non-photoactivated verteporfin (VP) can inhibit YAP-mediated tumor proliferation and angiogenesis by eliminating its interaction with TEAD. This study aimed to determine the effect and molecular mechanisms of VP-mediated inhibition of YAP in different subtypes of BC.MethodsLuminal A, Luminal B and Basal-like BC cells were cultivated in vitro to study effects of VP on proliferation and apoptosis of these three molecular BC subtypes.ResultsOur experimental results showed that VP inhibited cell proliferation, YAP-TEAD interaction and expression of its downstream targets. VP also induced tumor cell apoptosis, and promoted the cleavage of Caspase-9 and PARP in the cells of various molecular subtypes of BC.ConclusionThese findings provide a basis for the use of VP as a potential anti-tumor therapeutic for BC by targeting the Hippo pathway effector YAP.