Inhibition of Breast Cancer Regrowth and Pulmonary Metastasis in Nude Mice by Anti-gastric Ulcer Agent, Irsogladine

Abstract

Irsogladine is a commonly used anti-gastric ulcer agent in Japan, and recent in vivo studies have shown it to have anti-angiogenic properties. The exact role of irsogladine as an inhibitor of angiogenesis remains uncertain. In this study, we show that irsogladine inhibited breast cancer regrowth and pulmonary metastasis but had no anti-angiogenic function against HUVEC cells.Irsogladine failed to inhibit proliferation, tubular formation, and the uPA/MMP-1 mRNA expression of HUVEC cells. We also examined the effect of irsogladine in an orthotopic transplant model of human breast cancer metastasis in athymic mice. Human MDA-MB-435 cells were injected into the mammary fat pads. After nine weeks, the tumors were resected under general anesthesia. Irsogladine or vehicle was given p.o. daily thereafter. Daily administration of irsogladine at 120 mg/kg/day over a five-week period had no effect on the body weight of the mice. Tumor regrowth, average volume of pulmonary metastases, and the number of metastases were inhibited by 40, 48 and 64%, respectively. These results suggest that irsogladine may be useful in the breast cancer adjuvant setting.

The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods

“…It is shown that 2-hydroxy-4, 6-diamino- [1,3,5] triazines (a 1,3,5-Triazine derivative) have antiangiogenic property via potent inhibitory effect on VEGF-R2 tyrosine kinase (flk-1/KDR) that functions as the main mediator of VEGFinduced endothelial proliferation, survival, and migration (31). There areother studies in the literature about antiangiogenic effect of 1,3,5-Trazine different derivatives (32,33). Unlike the other members of 1,3,5-Triazinecompounds,there are no studies that provide evidence on the anticancer properties of methenamine salts, but formaldehyde released from methenamine in acidic PH can inhibit the proliferation and induce apoptosis of cancer cells (34).…”

Biochemical and Molecular Diagnostic Indicators for Cancer

“…MMPs have both pro-and antiangiogenic characteristics as a result. MMPs are required for angiogenesis in general, and MMP-1 has been shown to inhibit it in animal models [57][58][59].…”

A Systematic Review on Antitumor Agents with 1, 3, 5-triazines

“…Irsogladine ( Figure 22) has been shown to have anti-tumor activity in murine xenograft models of epidermoid cancer and glioma [152]. More recently, the effect of compound 64 was also investigated in a human breast cancer athymic nude mouse system and the results suggested that irsogladine can be useful in the breast cancer adjuvant setting [153].…”