Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats

Abstract

Breast cancer is among most common form of cancer worldwide. It is also the major cause of death in female cancer patient around the world. Despite various therapeutic measures, it remains associated with high mortality rate. Aegle marmelos (L.) Correa has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, there are very limited reports regarding its anticancer activity. Thus, the present research work has been aimed to study the anticancer activity of Aegle marmelos fruit extract on 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer in rats. Female Charles Foster rats, 55-60 days old weighing around (150 ± 10 g) were used for the study and were induced DMBA (20 mg/mL dissolved in Olive oil) orally. After the development of breast tumors (about 0.5 cm), the rats were treated with Aegle marmelos ethanolic fruit pulp extract (200 mg/kg b.w./day) orally for 5 weeks and then volume of tumor was measured. Aegle marmelos treatment showed significantly reduced mammary tumor volume (P < 0.05), along with significant reduction (P < 0.0001) in the different serum biomarkers such as TNF-α level, serum malondialdehyde (MDA) level and glucose levels. Significant (P < 0.0001) improvement in both, the kidney and liver serum biomarker parameters were also observed after the treatment with Aegle marmelos ethanolic fruit pulp extract. From the entire study, taking everything into account it can be interpreted that Aegle marmelos ethanolic fruit pulp extract possesses anti-proliferative activity by suppressing the progression of breast tumors in rat model. The plant extract also possesses hepato-renal protective effect. Hence, it can be targeted as novel and safe anti-cancer drug against breast cancer.

Figure 1

Gross photographs of rat mammary tumor of DMBA treated group (A,C) and Aegle marmelos treated group (B,D).

Figure 2

Effect of different treatments on tumor volume in the studied groups (n = 4, Significant P < 0.05, values are expressed as mean ± SEM).

Figure 3

Effect of different treatments on lipid peroxidation level in the studied groups (n = 4, Significant ***P < 0.0001 compared with control group, ^###P < 0.0001 compared with DMBA treated group, values are expressed as mean ± SEM).

Figure 4

Effect of different treatments on estradiol level in the studied groups (n = 4, P > 0.05 (NS), values are expressed as mean ± SEM).

Figure 5

Effect of different treatments on progesterone level in the studied groups (n = 4, P > 0.05 (NS) values are expressed as mean ± SEM).

Figure 6

Effect of different treatments on glucose level in the studied groups (n = 4, Significant ***P < 0.0001 compared with control group, ^###P < 0.0001 compared with DMBA treated group, values are expressed as mean ± SEM).

Figure 7

Effect of different treatments on serum TNF-α level in the studied groups (n = 4, Significant ***P < 0.0001 compared with control group, ^###P < 0.0001 compared with DMBA treated group, values are expressed as mean ± SEM).

Figure 8

Microphotograph of rat mammary tissue stained with hematoxylin and eosin. (A) Section of control rat mammary tissue showing normal arrangement of adipocytes (A) & duct (D) × 500. (B) Mammary tissue section of DMBA treated group rat showing dedifferentiated cells (DC) with the presence of mucin (M) in the ductal (D) lumen with discontinuous basement membrane × 500. (C,D) Mammary tissue section of Aegle marmelos treated group rat. Although, the ducts (D) basement membrane is discontinuous but there is absence of mucin and any other foreign substances while covered with thick mass of fibrous connective tissues (F) × 500.