126 (PB116) - Immunomodulatory effects of low piperine fractional Piper nigrum extract on breast cancer prevention

Abstract

Background: Piper nigrum, black pepper, has various biological effects such as anti-microbial, anti-inflammatory and anti-cancer activities. A crude extract of P. nigrum named low piperine fractional Piper nigrum extract (PFPE) has been reported for anti-tumor and anti-tumor immunity on breast cancer. PFPE also had an ability on cancer prevention. However, the mechanism of action of PFPE on cancer prevention has not been elucidated yet. Here, we evaluated the immunomodulatory role of PFPE on the prevention of breast cancer in mammary tumor rat model. Material and methods: Female Sprague-Dawley rats, 45 days old (virgin) were divided into 6 groups, including normal, control, vehicle (MCT and vitamin E) and PFPE at doses of 50, 100 and 150 mg/kg BW. Rats were injected with 250 mg/kg BW of NMU at 50 and 80 days old and fed with 100 μg/kg BW of estradiol after 7 days of 2nd NMU injection for 10 days. The PFPE was orally administered after 5 days of the 1st NMU injection, 3 times per week for 91 days. The blood from lateral tail vein was collected for cytokine study at 15 and 61 days after PFPE treatment. At the end of the experiment, rats were sacrificed and collected blood by cardiac puncture for investigation of blood parameters, ROS production, cytokines, chemokines and immune cell types. Internal organs were weighed, and tumor tissues were collected for histology study. Results: The cancer preventive effects of PFPE at a dose of 50, 100 and 150 mg/kg BW were 71.43, 71.43 and 100%, respectively. Meanwhile vehicle prevented breast cancer at 28.57%. There were no significant changes in organ/body weight ratio and blood parameters, except for alkaline phosphatase at a dose of 150 mg/kg BW. For the histological study, tumors of the control rats were invasive ductal carcinoma, while the rats treated with PFPE at doses of 50 and 100 mg/kg BW were ductal carcinoma in situ. In addition, PFPE treatment at a dose of 100 and 150 mg/kg BW represented amount of ROS higher than non-treated and vehicle groups. PFPE at doses of 50 and 150 mg/kg BW suppressed cytokines and chemokines compared to control and vehicle groups at 15 days after PFPE treatment. Moreover, PFPE at a dose of 100 mg/kg BW was the most effective dose at 61 and 91 days after treatment. Interestingly, all doses of PFPE stimulated IFN-γ at the endpoint of experiment. PFPE at doses of 100 and 150 mg/kg BW significantly promoted type 1 T helper cells and inhibited type 2 T helper cells and regulatory T cells compared to non-treated and vehicle groups. Conclusions: These results indicate that PFPE at doses of 100 and 150 mg/kg BW had efficacy on immunomodulation in cancer prevention through the regulation of ROS, Th1/Th2/Treg and cytokine/chemokine production. However, PFPE at a dose of 150 mg/kg BW should be carefully used for a long time due to its adverse effect on liver function. No conflict of interest.