Tranilast inhibits hormone refractory prostate cancer cell proliferation and suppresses transforming growth factor β1‐associated osteoblastic changes

Abstract

These observations suggest that tranilast may be a useful therapeutic agent for treatment of HRPC via the direct inhibitory effect on cancer cells and suppression of TGF-beta1-associated osteoblastic changes in bone metastasis.

Identifications of genetic differences between metastatic and non-metastatic osteosarcoma samples based on bioinformatics analysis

“…So, we inferred that OS pathogenesis may be related to wnt and Myc pathway abnormality and the genes in these functional nodes, such This result agreed with the findings of previous studies: TGFB1 involves in the osteoblastic changes in bone metastasis [19], and the differentiation of cancer cells to cancer stem cells in OS [20]; FLT3 could inhibit proliferation and promote cell death in OS cell lines [21]. Moreover, the metastatic and non-metastatic OS are closely related to KDM1A gene down-regulation, which is an evidence supporting the points that KDM1A is a therapeutic target for OS [22] and KRAS is a underlying target gene for OS treatment [23].…”

Tranilast: A review of its therapeutic applications

“…In a co-culture human scirrhous gastric cancer cell line, OCUM-2M with fibroblasts, which produce TGF-␤1, invasiveness, increased significantly and this effect was countered by tranilast [165]. In prostate cancer cells, this drug suppressed the secretion of TGF-␤1 from bone-derived stromal cells and inhibited TGF-␤1-associated differentiation of these cells [86].…”

“…Tranilast also suppressed the secretion of TGF-␤1 from bone-derived stromal cells, and inhibited TGF-␤1-associated differentiation of bone-derived stromal cells and osteoblastic changes [86]. To verify its clinical effect, in a pilot study by Izumi et al, tranilast exhibited benefit in the treatment and prognosis for patients with advanced castration-resistant prostate cancer (CRPC).…”

“…Since then, its inhibitory effects have been reported on the proliferation of a range of cell types: dermal fibroblasts [56,75], myofibroblasts [59], microvascular endothelial cells [76], vascular smooth muscle cells [77,78], and mesangial cells [79]. In addition to normal cells, tranilast exerts an anti-proliferative influence on several tumor cells, such as; smooth muscle cells hyperplasia [80], pancreatic cancer cells [81], uterine leiomyoma cells [82], malignant glioma cells [83], gastric cancer cells [84,85], prostate cancer cells [86], breast cancer cells [87][88][89], neurofibroma cells [90] and squamous cell carcinoma [58].…”

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

“…In addition, it was reported the ability of TN to downregulate TGF-beta production from bone stromal cells and other different cell types, thereby suppressing TGF- β -stimulated osteoclast differentiation which underlies, in part, osteoblastic bone metastasis [61, 166]. Noguchi et al [62] demonstrated that three weeks of TN treatment significantly reduced the tumor growth and metastasis, when administered daily by intraperitoneal injection (4 mg/animal), in a mouse model of oral squamous cell carcinoma.…”