Background and purpose: Viola odorata is a medical plant used in the treatment of hepatic disorders and relieving cancer pain. Melatonin (Mel) can act as an antioxidant and prevent cells against oxidative stress. This compound has a direct inhibitory effect on cancer cell proliferation. In the present study, we performed an in-vivo study to evaluate the effects of Viola odorata hydro-alcoholic extract (VOE) and MEL on tumor growth and NF-kB, TNFR1, and VCAM-1 expression rate in 4T1 breast cancer model.

Materials and methods: In this experimental study, 4T1 cells, which were cultured in-vitro, were harvested and put in a serum-free suspension medium. The animals (five groups, n=5) received subcutaneous injections of 0.1 ml of cell suspension (0.8 million cells) in the right mammary gland or hind flank. The implanted BALB/c mice with 4T1 cells were treated with different concentrations of VOE (50, 150, and 250 mg/kg) and Mel (40 mg/kg) for 21 days. The control group received distilled water. The mice were sacrificed on day 22. NF-kB, TNFR1, and VCAM-1 expression rate was measured by Western Blotting technique. To analyze the data, ANOVA test was run in SPSS, version 16.

Results: The size of tumors in Mel (P=0.000) and VOE250 (P=0.0001) treated mice was smaller compared to that of the control group. Our results indicated that Mel (P=0.022) and VOE250 (P=0.02) increased TNFR1 expression. On the other hand, Mel (P=0.034) and VOE150 (P=0.04) decreased VCAM-1 expression in the 4T1 breast cancer model. Unlike the Mel group, NF-kB expression reduced in the group receiving VOE250 compared to that of the control group (P=0.012).

Conclusion: It seems that VOE and Mel can reduce the rate of tumor growth in 4T1 breast cancer model by decreasing the expression of VCAM-1 and NF-kB and enhancing the expression of TNFR1.