Black pepper extract reduces tumour incidence via suppressing tumour <b>-</b> promoted cytokines <b>/</b> chemokines and modulating T cell subtype

Our study aimed to evaluate tumour retardation effects of low-piperine fractional Piper nigrum extract (PFPE or LP-PE) related to enhancement of immune response. Results showed that PFPE at doses of 50 (low), 100 (intermediated) and 150 (high) mg/kg BW had a tumour incidence of 20, 20 and 0%, respectively. PFPE at low dose inhibited cytokines/chemokines in the early stages of cancer however it could not suppress longer than 3 months. Intermediated dose of PFPE inhibited cancer cytokines/chemokines including sICAM-1, CX3CL1, CXCL7, VEGF, TIMP-1, CCL5, CCL20, CXCL1, CXCL5, CXCL9 and IL-1β. Interestingly, PFPE stimulated IFN- γ at 3 months after treatment in all doses. Intermediated and high doses of PFPE increased Th1 and reduced Th2. Moreover, only a high dose of PFPE reduced Treg. Additionally, PFPE reduced ER-α and NF-κB and increased IL-6R and STAT3 proteins in tumour tissues. Our findings indicate that PFPE suppressed breast cancer via immune modulation.