Towards Drug Repurposing Olsalazine As A Hypomethlating Compound For The Treatment of Breast Cancer

Abstract

Aim and Objective: Breast Cancer is the carcinoma of the breast. It is the second most common cancer in women worldwide. By similarity search and various docking studies, it was found that olsalazine can act as a demethylating agent who helps in reducing tumor growth and invasiveness. Therefore, the objective of our study was pharmacological evaluation of olsalazine for the treatment of breast cancer. Material and Methods: Induction of the study was carried out by the administration of 7,12 Dimethyl Benz(α) Anthracene (DMBA) once at a dose of 45 mg/kg by subcutaneous route in mammary glands of rats in DMBA induced breast cancer model. After 16 weeks of induction, 7 days of treatment was given and blood was collected for determination of biochemical parameters. In the end, animals were sacrificed and tumors were isolated and morphological parameters, immunohistochemistry and histopathology was carried out. In Xenograft Model, 5*105 cells were injected into the mammary glands of mice. After 4 weeks of induction, 7 days of treatment was given and blood was collected for determination of biochemical parameters. In the end, animals were sacrificed and tumors were isolated and morphological parameters, histopathological studies and tumor specific parameters were carried out. Results: In morphological evaluation, we have found that there was statistically significant reduction in the tumor volume in animals treated with olsalazine in comparison to diseased animals. In our study, in DMBA induced breast cancer model we have found reduced levels of various biochemical parameters (LDH, CKMB, CRP, TP, SGPT, SGOT, and creatinine) in olsalazine treated groups in comparison to disease control group. In immunohistochemical studies, p53 levels were found to be decreased in the olsalazine treated group in comparison to disease control group. Anticancer effect of olsalazine was seen in various tumour specific parameters. In xenograft model, various biochemical parameters such as LDH,CRP, Total protein,SGPT levels etc. were raised in diseased animals and marked decrease was found in drug treated animals. In histological studies, protective effect of olsalazine was clearly visible in olsalazine treated animals. Conclusion: From the present study, we can conclude that olsalazine has potential in the treatment of breast cancer by virtue of its demethylating activity in both DMBA induced breast cancer model as well as in Xenograft model.