Clostridium botulinum neurotoxin A inhibits DBTRG glioblastoma cell proliferation and TRPV1 channel signaling pathways

Abstract

Prevalence of glioblastomas is high within the adult brain tumors and the proliferation of the glioblastomas was induced by excessive Ca2+ influx. Ca2+ permeable TRPV1 channel is gated by capsaicin and reactive oxygen species (ROS), although its activity was decreased in neurons by AMG and antioxidants. Clostridium
 botulinum neurotoxin A (BotxA) acted antioxidant action in several cells and its treatment modulated TRPV1 in neurons. Hence, treatment of BotxA may modulate
 glioblastoma cell proliferation and death via inhibition of TRPV1 in the DBTRG glioblastoma in vitro cell line model. The DBTRG cells were divided into three groups as control, BotxA (5 IU for 24 hours) and BotxA+TRPV1 channel blocker (AMG and 1 µM for 30 min). Intracellular Ca2+ response to TRPV1 activation was increased in the cells from capsaicin, although it was reduced by the BotxA and AMG. BotxA treatment decreased cell proliferation, although its treatment increased cell death (propidium iodide/Hoechst rate). In addition, BotxA decreased mitochondrial membrane depolarization levels, cytosolic and mitochondrial ROS generation in the cells. Their levels were further decreased in the BotxA+AMG group by the AMG treatment. The antiproliferative and neurotoxic effects of BotxA were shown to be exerted via modulation of oxidative stress and TRPV1 activation. BotxA could be used as an effective agent in the treatment of glioblastoma proliferation.