Targeting Mast Cells Tryptase in Tumor Microenvironment: A Potential Antiangiogenetic Strategy

Table 3

All studies mentioned above that have considered tranilast.

Author, reference, year	Drug/s	Tumor target	Molecular mechanisms of action	Results
Chakrabarti et al. [57] 2009	tranilast	several mouse, rat and human breast cancer cell lines	(1) down-regulation of TGF-β pathway; (2) inhibition of MAPK pathway	inhibition of tumor cell proliferation, angiogenesis, apoptosis, migration
Subramaniam et al. [58] 2010	tranilast	mouse breast cancer cell line (4T1)	(1) down-regulation of TGF-β pathway; (2) induction cell arrest in the G0/G1 transition, PARP cleavage, AKT1 phosphorylation; (3) up-regulation of p53; (4) reduction of ERK1/2 phosphorylation	inhibition of tumor cell proliferation, angiogenesis, apoptosis, migration
Hiroi et al. [59] 2002	tranilast	hamster pancreatic cancer cell line (PGHAM-1)	(1) down-regulation of TGF-β pathway with reduction of MMP-9 and VEGF levels; (2) induction cell arrest in the G0/G1 transition	inhibition of tumor cell proliferation, angiogenesis
Mitsuno et al. [60] 2010	(1) tranilast plus gemcitabine; (2) gemcitabine	human pancreatic cancer cell line (KP4)	decrease of RRM1 expression	(1) inhibition of tumor cell proliferation, angiogenesis, apoptosis; (2) synergistic cytotoxic effect of combination therapy
Izumi et al. [61] 2009	tranilast	(1) prostate cancer cell lines and bone-derived stromal cells; (2) SCID mice; (3) advanced hormone-refractory prostaste cancer (21 pts)	down-regulation of TGF-β1 pathway	(1) induction of apoptosis; (2) reduction of invasion and bone metastasis, PSA levels, improve prognosis
Noguchi et al. [62] 2003	tranilast	mouse model of oral squamous cell carcinoma	not analyzed	decrease of tumor growth, angiogenesis, cervical lymph node metastases
Yashiro et al. [63] 2003	tranilast	human gastric carcinoma cell line (OCUM-2D) and gastric fibroblast cell line (NF-10)	down-regulation of TGF-β pathway	decrease of tumor growth, angiogenesis, invasion
Platten et al. [64] 2001	tranilast	human malignant glioma cell line	down-regulation of TGF-β1-2 pathway	decrease of tumor growth, angiogenesis, migration, invasion
Nie et al. [65] 1997	tranilast	breast cancer cell lines (MCF-7)	induction cell arrest in the G0/G1 transition	decrease of tumor growth
Subramaniam et al. [66] 2011	tranilast	human breast cancer cell lines (triple positive-BT-474, triple negative-MDA-MB-231)	(1) up-regulation of p53; (2) induction cell arrest in the G0/G1 transition, AKT1 and ERK2 phosphorylation, PARP-cleavage product	induction of apoptosis, tumor growth, migration
Zhang et al. [67] 2009	tranilast	several ER negative human breast cancer cell lines	agonizing ARH with down-regulation of TGF-β and NF-κB pathways	(1) induction of apoptosis; (2) inhibition of angiogenesis, cell growth, invasion and metastasis
Hall et al. [68] 2010	tranilast	several human breast cancer cell lines	agonizing ARH with down-regulation of TGF-β and NF-κB pathways	(1) induction of apoptosis; (2) inhibition of angiogenesis, cell growth, invasion and metastasis
Isaji et al. [69] 1997	tranilast	human pancreatic cancer cell lines	decrease of VEGF and MMPs levels	inhibition of angiogenesis, cell growth, migration

TGF-β1, Tumor growth factor-beta1, MMPs, metalloproteinases; MAPK, mitogen-activated protein kinase uPA, PARP, poly ADP-ribose polymerase; urokinase-type plasminogen activator; AKT1, RAC-alpha serine/threonine-protein kinase; ERK, Extracellular regulated kinase 2; VEGF, Vascular endothelial growth factor; RRM1, Ribonucleotide reductase M1.