Pharmacological Action of C-Phycocyanin In Experimentally Induced Breast Cancer In Rats

Abstract

Background: Breast cancer is the second most common cause of death among women worldwide, after lung cancer. It occurs when certain cells in the breast become abnormal and uncontrollably multiply to form a tumor. This phenomenon arises because of various genetic and environmental factors that activate multiple pathways, such as Ras/Raf, PI3k/Akt, and Wnt. Phycocyanin, a microalgae- derived protein obtained from Arthrospira plantensis (commonly known as Spirulina), exhibits protein-binding activity and imparts a blue color. C-phycocyanin has antioxidant, antiinflammatory, and anticancer properties. Aim and objectives: The objective of the present study was to investigate the pharmacological action and mechanism of action of C-phycocyanin on 7, 12-dimethylbenz[a] anthracene (DMBA) induced breast cancer in female Wistar rats. Materials and Methods: The experiment involved inducing breast cancer was induced in Wistar female rats by administering a subcutaneous injection of 7, 12-dimethyl benz [a] anthracene (35 mg/kg) in the mammary gland. The rats were divided into six different groups according to their treatment regimen. Standard treatment involved the use of doxorubicin (4 mg/kg), while Cphycocyanin (at doses of 40, 80, and 120 mg/kg) was used as an investigational drug. Cancer was induced in the rats for 12 weeks, followed by treatment with standard or investigational drugs for four weeks. After completion of treatment, the rats were euthanized using thiopental sodium, and the tumors were collected for analysis. The study evaluated tumor-specific parameters (tumor volume), oxidative stress parameters (glutathione reductase and malondialdehyde levels), inflammation markers (IL-1β), and genetic expression of AMPK and PI3K were evaluated. A histopathological evaluation was performed. Results: Our results indicate that the administration of C-phycocyanin (80 mg/kg) did not reduce the tumor volume as compared to the doxorubicin 4 mg/kg group. Additionally, GSH levels were increased in all the treatment groups as compared to disease control group. Furthermore, the DMBA-treated (DC) group exhibited higher levels of malondialdehyde than the NC group, indicating increased lipid peroxidation. However, administration of doxorubicin (4 mg), Cphycocyanin (40 mg), and C-phycocyanin (80 mg) resulted in a significant reduction in MDA levels compared to the DC group. Furthermore, the doxorubicin 4 mg group exhibited a significant decrease in IL-1β levels as compared to the disease control group. However, the administration of C-phycocyanin at doses of 40, 80, and 120 mg led to a significant increase in IL-1β levels as compared to the DC group. Histological analysis revealed the presence of viable tumor cells in the groups treated with DMBA (DC), doxorubicin (4 mg), and Cphycocyanin (40 mg), but no necrosis was observed in any of the groups. Additionally, inflammation was observed in all groups, whereas the normal control group had parenchymal and interstitial tissues. Conclusion: Based on literature, C-phycocyanin has shown stimulated apoptotic anti-cancer activity in various In-vitro studies on MDA-MB-231 TNBC cell line as well as in xenograft models. However, we failed to mirror the similar effects in In-vivo DMBA induced breast cancer in rats. Results obtained from the study also demonstrated that C-phycocyanin has not shown any significant change in tumor progression, reduction in oxidative stress and inflammation.