Tranilast suppresses prostate cancer growth and osteoclast differentiation in vivo and in vitro.

Abstract

BACKGROUND:

In bone metastatic sites, prostate cancer cells proliferate on interacting with osteoclasts. Tranilast, which is used for an antiallergic drug, has been shown to inhibit growth of several cancers and stromal cells. The present study was conducted to assess suppressive effects of Tranilast on prostate cancer growth and osteoclast differentiation in vivo and in vitro.

METHODS:

In vivo, rat prostate cancer tissue was transplanted onto cranial bones of F344 rats and Tranilast was given for 9 days at doses of 0, 200, or 400 mg/kg/day. In vitro, human prostate cancer cell lines, LNCaP, PC3, and DU145, the rat prostate cancer cell line, PLS-10, and rat bone marrow cells were similarly treated with the agent.

RESULTS:

In vivo, tumor volumes were significantly decreased in the high dose group. While cell proliferation did not appear to be affected, apoptosis was induced and tumor necrosis was apparent. Cranial bone defects were decreased in the high dose group. In vitro, cell proliferation rates of all four cell lines were reduced by Tranilast and increased apoptosis was observed in LNCaP and PLS-10. In addition, Tranilast significantly reduced osteoclast differentiation of rat bone marrow cells. Western blot analysis of PLS-10 and LNCaP revealed that phospho-GSK3beta was up-regulated and phospho-Akt was down-regulated.

CONCLUSIONS:

Tranilast here suppressed rat prostate cancer growth and osteoclast differentiation. Growth of human prostate cancer cells was also inhibited. Thus, this agent deserves consideration as a candidate for conventional therapy of bone metastatic prostate cancer.

• Authors: Shinya Sato, Satoru Takahashi, Makoto Asamoto, Taku Naiki, Aya Naiki-Ito, Kiyofumi Asai, Tomoyuki Shirai
• Journal: The Prostate (Prostate) Vol. 70 Issue 3 Pg. 229-38 (Feb 15 2010) ISSN: 1097-0045 [Electronic] United States
• PMID: 19790239 (Publication Type: Journal Article)
• Copyright: Copyright 2009 Wiley-Liss, Inc.

Chemical References

• ortho-Aminobenzoates
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• tranilast

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Bone Marrow Cells (cytology)
• Bone Neoplasms (drug therapy, secondary)
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Down-Regulation
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Male
• Necrosis
• Neoplasm Invasiveness (pathology)
• Neoplasm Transplantation
• Osteoclasts (cytology)
• Phosphorylation (drug effects)
• Prostatic Neoplasms (pathology, physiopathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Inbred F344
• Skull
• Up-Regulation
• ortho-Aminobenzoates (administration & dosage)