Botulinum Toxin Type A Inhibits the Growth of LNCaP Human Prostate Cancer Cells In Vitro and In Vivo

Abstract

BTA inhibits the growth of LNCaP human PCa cells in vitro and in vivo. These findings indicate that intra-prostatic BTA injections to treat BPH are unlikely to promote the growth of co-existing infra-clinical PCa foci in men. A potential inhibitory effect of BTA on the growth of human PCa should be further studied.

Synaptic Vesicle Protein 2 (SV2) Isoforms

“…The role of SV2 in breast cells could be associated to secretory nature of mammary glands, and may interact with other vesicle proteins such as synaptobrevin, which is essential for secretion but not for the development of synaptic process (Ahnert-Hilger et al, 1996), however, the SV2 role in cancer is not clear, although it is already reported in others types of cancer, for instance, brain (de Groot et al, 2010;, pancreas (Jakobsen et al, 2002), gastrointestinal tract (Jakobsen et al, 2002;Bumming et al, 2007 ), liver (Hanoun et al, 2010), bladder (Coelho et al, 2010), prostate (Karsenty et al, 2009) and adrenals (Li et al, 1999) tumors among others, where SV2 has already been proposed as molecular and transdifferentiation marker of neural nature (Nilsson et al, 2004;Zhang et al, 2010). This is possible because in the cancerous state the terminal differentiation to the anticipated cellular type is altered and the phenomena of lineage infidelity that is associated with the ability of cancer cells to transdifferentiate, occurs in different cancer types and occur in breast cancer (Zhang et al, 2010); thus, it is a commune phenomenon that cancer cell turns-off/-on non-habitual genes changing the ontogeny to evade the immune system and hold the linage independence.…”

“…SV2 expression can have a double importance as cancer molecular marker (Zhang et al, 2010) and therapeutic use in malignity due SV2 leads the entry of BoNTA, which has anti-proliferative, pro-apoptotic and quimiodenervation functions in prostate cancer (Arnon et al, 2001;Dong et al, 2006;Choi et al, 2007;Karsenty et al, 2009;Hanoun et al, 2010;Zhenzhen et al, 2012) that could be extrapolate to breast tumors. BoNTA is recognized by SV2 receptors in neurons.…”

“…The presence of secretory vesicles is characteristic in synaptic (de Groot et al, 2010;, gastric (Bumming et al, 2007), pancreatic (Jakobsen et al, 2002), adrenal (Li et al, 1999) and prostatic (Karsenty et al, 2009) cells which synaptic vesicular receptor (SV) play an important role in exocytosis and secretory process of synaptic (de Groot et al, 2010) and endocrine cells, (Dong et al, 2006;Coelho et al, 2010), but when cancer occurs this protein tends to overexpress in brain (de Groot et al, 2010), neuroendocrine (Portela-Gomes et al, 2000), gastrointestinal (Bumming et al, 2007) and prostate (Karsenty et al, 2009) is not clear neither it has been reported in breast cells, but its role as molecular marker of cancer in others organs and tissues has been increasing in recent years (Portela-Gomes et al, 2000;Zhang et al, 2010).…”

“…The importance of SV receptors is more evident when this cellular membrane receptor is bound to neurotransmissors, drugs and neurotoxins, such as tetanus toxin and botulinium neurotoxin (BoNTA), especially the type A (BoNTA), that in therapeutic doses and for endocytosis lets to improve conditions as epilepsy and cancer in a more specific manner (Arnon et al, 2001;Karsenty et al, 2009;de Groot et al, 2010;Montal, 2010;Blum et al, 2012;Shi et al, 2011) and lead to apoptosis (Choi et al, 2007). BoNTA has been successfully used in the treatment of refractory detrusor overactivity.…”

“…In the cytoplasm, BoNTA cleaves specific sites of synaptosomal-associated protein 25 (SNAP-25), preventing the assembly of the synaptic fusion complex SNARE and blocking exocytosis (Simpson, 1979;Chancellor et al, 2008;Coelho et al, 2010). Thus, BoNTA inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo (Karsenty et al, 2009). …”