Exploration of α-Glucosidase Inhibitor for the treatment of Diabetes associated Breast Cancer

Abstract

Background: Scientific evidence suggests that hyperglycemia is associated with different types of cancers. Many studies have concluded that women with diabetes mellitus are at higher risk of developing breast cancer than women with no diabetes mellitus. mTOR pathway is found to be upregulated in the hyperglycemic state, which is also responsible for cell growth and cell proliferation. α-Glucosidase inhibitors show their inhibitory effects on the mTOR pathway. Therefore, the objective of the present study was to evaluate the preventive effect of the α-Glucosidase inhibitor on the diabetes-associated breast cancer model via targeting the mTOR pathway.

Method: Forty-two animals were allocated to six different groups: Normal Control (NC), Diabetes Control (DC), Breast Cancer control (CC), Diabetes-Breast Cancer Control (DC-CC), Diabetes-Breast cancer control group was treated with metformin at a dose of 500 mg/kg p.o. daily (DC-CC+MET), and the Diabetes-Breast cancer control group was treated with Voglibose at a dose of 10 mg/kg p.o. daily (DC-CC+VOG) till the study end. A single intraperitoneal injection of streptozotocin at a dose of 35mg/kg was administered for diabetes mellitus induction followed by breast cancer induction by administrating the single subcutaneous administration of 7,12-dimethylbenz[a]anthracene (DMBA) at 35 mg/kg in the mammary fat pad of the female Sprague-Dawley rats. Treatment was started after two days of DMBA administration for 21 days. Bodyweight, food intake, water intake, tumor incidence, and tumor volume were determined for 4 weeks. At the end of 4 weeks, blood was collected for the determination of biochemical parameters, and animals were sacrificed for histopathological, and immunohistochemical studies.

Results: In morphological evaluation, we observed the reduced tumor volume of the diabetesbreast cancer control group which was administered Voglibose when compared to the diabetesbreast cancer control group. Treatment has also shown an improvement in the body weight, food, and water intake parameters. LDH, GGT, ALP, and CRP levels were also found to be increased in the disease control group and found to be reduced significantly after the treatment with Voglibose. Furthermore, the Diabetes-Breast Cancer group showed an elevated level of MDA and reduced activity of SOD, catalase, and GSH in mammary tissues. Oraladministration of Voglibose prevents overproduction of MDA and restores the antioxidant activities of enzymes. Results of histopathological examination showed that the disease control group consists of more neutrophil infiltration when compared to the normal control group. However, the neutrophil infiltration got reduced in Voglibose treated group compared to the disease control group. Immunohistochemistry results showed that there is reduced cell proliferation in Voglibose treated group as compared to the disease control group.

Conclusion: From this study, we have concluded that Voglibose has a preventive effect on diabetes-associated breast cancer.