Pharmacological Evaluation of Anticancer Activity of Celastrus Paniculatus Against Experimentally Induced Breast Cancer in Rats

Abstract

Background: Breast tumors occur when some cell in the breast becomes abnormal as well as multiply uncontrollably to form a tumor. Breast cancer is second frequent causes of death across the globe. In 2019, in U.S. about 2, 45,000 cases of breast malignancy are diagnosed in women as well as 460 men in the United States pass away every year from breast malignancy. The genetic factor as well as environmental factors is responsible for breast malignancy. There are diverse types of pathways responsible for breast malignancy as Ras/Raf, PI3k/Akt/mTOR pathways and Wnt pathway. The drug Celastrus Paniculatus is acting on Akt pathways which is a signal transduction pathway that stimulates survival as well as growth responses to extracellular signal. Aim and Objectives: The objectives of the current study were to examine pharmacological actions of Celastrus paniculatus as well as to investigate the mechanism of action of Celastrus paniculatus against experimentally induced breast cancer in female Wistar rats. Materials and Methods: 25 mg/kg of DMBA was dissolved in 1 ml of Olive oil and injected by SC route below the mammary gland on the right part by single dosing for induction of breast cancer. The animals were divided in 6 groups. The induction was confirmed by histopathology, at the ending of 12th weeks. The animals were subjected to the assigned treatment as per the protocol and standard drug (Cisplatin (4 mg/kg)) as well as test drug (Celastrus Paniculatus (100, 200 as well as 400 mg/kg)) were administered for 4 weeks. At the ending of 16 weeks of the study, the animals were sacrificed as well as tumors were histopathological and biochemical analysis. Inflammatory biomarkers such as Caspase 3, p53, VEGF, IFN-ү, TNF-α and IL-1β were also performed.Results: Inflammatory markers: It was seen that there was increase in VEGF, IL-1β and IFN-ү levels (p<0.05) in disease group animals as compared with normal group animals. It was also seen that there was decrease levels of inflammatory markers in disease group animals as compared treated group animals. Apart from this it was also seen that levels of Caspase 3, VEGF, IL-1β, p53 and IFN-ү found to be increase in Celastrus Paniculatus 400mg (p<0.01) as compared with treated group animals of 100 mg as well as 200 mg. Apart from this it was also seen that levels of Caspase 3, VEGF, IL-1β, p53 and IFN-ү found to be increase in Standard (p<0.01) group animals as compared with Celastrus Paniculatus 100 mg, 200 mg as well as 400 mg. Tumor specific parameters: Tumor volume: It was seen that there was increase in tumor volume of disease control group (p<0.001) as compared with Standard control group treated with Cisplatin. It was also seen that there was decrease in tumor volume of Celastrus Paniculatus 400 mg (p<0.01) group animals as compared with Celastrus Paniculatus 100 mg as well as 200 mg. Apart from this it was also seen that the tumor volume of Standard control group treated with Cisplatin (p<0.05) increase as compared with Celastrus Paniculatus 100 mg, 200 mg and 400 mg group animals. It was also seen that the tumor volume of disease control group treated (p<0.001) increase as compared with Celastrus Paniculatus 100 mg, 200 mg and 400 mg group animals. Histopathological Evaluation: Histological evaluation figures showed that there was occurrence of tumors cells as well as inflammation in DMBA control group animals. Furthermore, there was no tumor, inflammation or cell necrosis seen in Cisplatin group animals. While, it was found that inflammation as well as necrosis was seen in other treated group animals. Conversely, animals treated with Celastrus Paniculatus showed occurrence of feasible cells of tumor as well as inflammation as well as cell necrosis. Conclusions: Our data is suggestive that drug Celastrus Paniculatus shows anticancer activity against DMBA induced breast cancer model in rats. This may be due to the inhibitory effect on inflammatory markers like IL-6, IL- 1β, Caspase 3, and p53, IFN-ү, VEGF and TNF- α.