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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. [ABSTRACT FROM AUTHOR]

Context: Many natural extracts have been shown to minimize the toxicity of doxorubicin (Dox). Low piperine Piper nigrum L. (Piperaceae) extract (PFPE) is a natural extract containing many types of antioxidants that may reduce Dox toxicities. Objective: To evaluate the effect of PFPE in attenuating the side effects of Dox. Materials and methods: Tumour-bearing Sprague Dawley rats were divided into five groups including normal, vehicle, 100mg/kg BW of PFPE plus 2mg/kg BW of Dox (P100þDox), 100 mg/kg BW of PFPE plus 2mg/kg BW of Dox (P200þDox) and Dox. Rats were treated with Dox and/or PFPE three times/week for 4 weeks. Tumour burden, blood parameters, weight of internal organs and immunological data were investigated. Results: The addition of 200 mg/kg PFPE significantly restored the levels of AST from 174.60 ± 45.67 U/L in the Dox group near to normal levels at 109.80 ± 4.99 U/L. The combination of PFPE and Dox also decreased the levels of CXCL7, TIMP-1, sICAM-1 and L-selectin about 1.4-1.6-fold compared to Dox group. Feeding rats with 200mg/kg BW of PFPE combination with Dox slightly increased Th1 from 161.67 ± 14.28 cells in Dox group to 200.75 ± 5.8 cells meanwhile suppressed Treg from 3088 ± 78 cells in Dox to 2561 ± 71 cells. Discussion and conclusions: This study showed that PFPE ameliorated Dox toxicity in many aspects indicating the role of antioxidant and other substances in the extract on toxicity attenuation. This suggested the using of PFPE may be valuable for Dox treated patients. [ABSTRACT FROM AUTHOR]

Background: Black pepper (Piper nigrum L.) is widely used as a traditional medicine, including usage for pain relief, fevers, as well as an anticancer agent. Previously, we reported that piperine-free P. nigrum extract (PFPE) inhibited breast cancer in vitro and in vivo. Objective: In this present study, we explored the anticancer effects of PFPE on cholangiocarcinoma (CCA). Materials and Methods: 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to analyze cytotoxic potential of PFPE whereas deoxyribonucleic acid (DNA) fragmentation followed by Western blot analysis were used. Results: PFPE composed of alkaloid, flavonoid, amide, lignans, opioid, and steroid. This crude extract represented cytotoxic effect against CCA cells which stronger than dichloromethane P. nigrum crude extract and piperine, especially on KKU-M213 (median inhibition concentration [IC50] at 13.70 μg/ml) and TFK-1 (IC50at 15.30 μg/ml). Interestingly, PFPE showed lower cytotoxicity against normal human cholangiocyte MMNK-1 cells (IC50at 19.65 μg/ml) than KKU-M213 and TFK-1 cells. Then, the molecular mechanisms of PFPE were firstly evaluated by DNA fragmentation followed by Western blot analysis. The degradation of DNA was observed on KKU-M213 and TFK-1 cells after treatment with PFPE at day 2. Then, proliferation proteins including topoisomerase II, AKT8 virus oncogene cellular homolog, avian myelocytomatosis virus oncogene cellular homolog, cyclin D1, signal transducer and activator of transcription 3, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were decreased and p21 was increased. Furthermore, apoptotic proteins, such as tumor protein p53, Bcl-2-associated X protein, and p53 upregulated modulator of apoptosis were upregulated. Meanwhile, antiapoptotic protein B-cell lymphoma 2 was down-regulated. Conclusion: These results indicated that PFPE inhibited CCA through the down-regulation of cell proliferation and induction of apoptosis pathway. [ABSTRACT FROM AUTHOR]