Table 3.

In vivo and in vitro effects of BoNT injection on malignant tumors and cancer cell lines.

Authors	Study Type	Type of Cells or Tissue	Study Design	Results
Vezdrevanis 2011 [57]	In vivo	Prostatic cancer	Injected BoNT into prostate	Tumor size reduction
Ulloa et al., 2015 [58]	In vivo	Glioblastoma cells	Cells with or without transfection by BoNT-C1 injected into mice striatum	By BoNT-C1 blocks the growth of Glioblastoma cells via blocking Syntaxin1
He et al., 2016 [59]	In vivo	Mice with pancreatic tumor	Injected onaA or saline into tumor	Reduced tumor size; increased apoptosis
Karsenty et al., 2009 [60]	In vitro	Prostate LNCaP and PC-3 cell lines	LNCaP and PC-3 cell lines were exposed to onaA	OnaA inhibited LNCasP cell proliferation; had no effect on PC-3 cell
Nam et al., 2012 [61]	In vitro	Breast and colorectal cancer	PLC-γl-transformed cells were exposed to BoNT-A (difficile)	Caused apoptosis and mitotic inhibition
Proietti et al., 2012 [62]	In vitro	Prostate LNCaP and PC-3 cell lines	Prostate cancer cell lines were exposed to incoA	Tumor cell growth slowed down probably due to toxin effect on SV2 receptors
Bandala et al., 2013 [63]	In vitro	Breast T47D cancer cells	Breast T47D cancer cells were exposed to diverse dilutions of BoNT	BoNT via caspase 3, slow down the growth of T47d cells and caused apoptosis
Bandala et al., 2015 [64]	In vitro	Breast cancer cell line	Added BoNT-A to breast cancer cell line	BoNT-A diminished SV2 protein on the surface of breast cancer cells
Rust et al., 2016 [65]	In vitro	Human neuroblastoma cells	Added BoNT-C to human neuroblastoma cell culture	Apoptosis of neuroblastoma cells
Huang et al., 1998 [66]	Invitro	Insulin secreting HIT-T15 cells	Insulin secreting cells were transfected by BoNT-A	Marked reduction of insulin secretion- potential to treat insulinoma
Hajighasemlou et al., 2015 [67]	In vitro	Her2 positive breast cancer cell line	Assessed the effect of BoNT-A on Her2 positive cells responsive to Herceptin	Herceptin efficacy significantly improved
Cheng et al., 2013 [68]	In vitro and in vivo	Prostate cancer cell line in Mice	LNCaP and PC3 cancer cells were exposed to 1 to 10 units of onaA	No effect on tumor growth in LNCaP and PC3 cancer cells
Ansiaux et al., 2006 [69]	In vivo	Fibrosarcoma, hepatosarcoma	BoNT-A injected into the tumor	Increased oxygenation of the tumor and made it more susceptible to chemo and radiotherapy
Coarfa et al., 2017 [70]	In vivo	Prostate of 250 nude mice Four human cancerous prostates	Effect of onaA versus saline injection into cancer cells implanted into rodent’s prostate Assessed the effect of onaA versus saline injection in cancerous prostate before prostatectomy	Increased apoptosis; slowed cancer progression Increased apoptosis in ona-A injected side of prostate

OnaA: OnabotulinumtoxinA (Botox). IncoA: IncobotulinumtoxinA (Xeomin).