Abstract A68: Penfluridol suppresses triple-negative breast cancer metastasis to brain by inhibiting integrin signaling

Breast cancer is the second leading cause of cancer related deaths in US. Breast tumor metastasis to brain is major cause of deaths. Brain metastasis of triple negative breast cancer cells (TNBC) is highly resistant to current therapies and is a cause of reduced survival rates in patients. In current study, we evaluated penfluridol, a first generation, highly potent antipsychotic drug against three different highly aggressive TNBC cell line. The IC50 of penfluridol was around 6 µM in 4T1, MDA-MB-231 and HCC-1806, breast cancer cells respectively. Our result showed that the expression of integrinβ4, integrinα6, Fak, Paxillin, Rac1/2/3 and ROCK1 was significantly reduced after 24 hours of treatment with penfluridol. We also observed that penfluridol treatment induced significant apoptosis in 4T1, MDA-MB-231 and HCC-1806, TNBC cells as exbited by cleavage of caspase 3. Interestingly, integrin signaling is known to play significant role in breast cancer metastasis and integrinα6β4 are overexpressed in breast tumors. Integrinα6 and β4 were silenced in breast cancer cells using shRNA and siRNA respectively. Silencing integrinα6β4 resulted in apoptosis which was further increased by penfluridol treatment. On the other hand, activation of integrins by TGFβ treatment and Laminin reduced induction of apoptosis by penfluridol confirming the role of integrins. We further evaluated the efficacy of penfluridol in three independent invi...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research