Inotodiol suppresses proliferation of breast cancer in rat model of type 2 diabetes mellitus via downregulation of β-catenin signaling

Posted 4 years ago in topic Healthcare

Author: Xia Zhang,Cuiyu Bao,Jingping Zhang
Publication: Biomedicine & Pharmacotherapy
Publisher: Elsevier
Date: March 2018

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Abstract

Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroomInonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of7,12-dimethylbenz(a)anthracene(DMBA) at 10 mg/kg. Diabetes development in experimental rats was confirmed by measuring fasting blood glucose levels andoral glucose tolerance test (OGTT), and other biochemical assays were performed. Histological evaluation of pancreas was performed. The proliferation of breast tumor was measured by immunohistochemical staining for PCNA, cleaved-caspase-3 and TUNEL stainingforapoptosis, andβ-catenin. Results of the study demonstrate that inotodiol lowered the blood glucose levels in SD rats as well as reduced plasma levels of cholesterol,triglyceride, and high-density lipoprotein. The tumor proliferation marker PCNA was reduced by inotodiol. It downregulated the expression of β-catenin and its downstream targets (c-Myc and Cyclin D1) followed by apoptosis induction. Conclusively, results suggest that inotodiol regulates blood glucose levels in diabetic rats and then controls proliferation of breast tumor progression by inducing apoptosis via downregulation of β-catenin signaling. It further suggests that inotodiol can be a preventive approach in managing dietary chronic conditions like diabetic-breast cancer.

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