title: Anti-cancer effects of Piper nigrum via inducing multiple molecular signaling in vivo and in vitro.
abstract: BACKGROUND
  Piper nigrum is widely used as a folk medicine including usage for pain relief, fevers, as well as an anti-cancer agent. However the crude extract of piperine free P. nigrum (PFPE), which inhibits breast cancer, and its mechanisms are still being kept secret. This research aims to elucidate the anti-cancer effects of PFPE and its mechanisms.
  
  
  METHODS
  Anti-cancer effects of PFPE were investigated in N-nitroso-N-methylurea (NMU)-induced mammary tumorigenesis rats and breast cancer cell lines MCF-7 and ZR-75-1. Furthermore, the cancer prevention effects of PFPE were investigated in rats. Western blotting was employed to study protein levels induced by PFPE.
  
  
  RESULTS
  PFPE was found to up-regulate p53, and down-regulate estrogen receptor (ER), E-cadherin (E-cad), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), c-Myc, and vascular endothelial growth factor (VEGF) levels in breast cancer rats. Moreover, PFPE decreased protein levels of E-cad, c-Myc, and VEGF in MCF-7 cells. These results suggest that PFPE can enhance breast cancer cell response to phytochemicals, then induce cell cycle arrest, and inhibit cancer cell proliferation resulting in tumor size decrease in the PFPE treated group. It further suggests that PFPE may suppress tumor cell invasion, migration, and angiogenesis. In addition, PFPE possessed cancer prevention effects through generation of reactive oxygen species (ROS) to higher cancer cell cellular stress.
  
  
  CONCLUSIONS
  PFPE may possess anti-cancer and cancer prevention effects; hence, it deserves further investigation as a novel candidate for breast cancer treatment.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; Yunnan Institute of Parasitic Diseases, Puer, Yunnan 65900, PR China. Electronic address: dy28@foxmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand. Electronic address: somchai.sr@psu.ac.th.
authors.forename: Somchai
authors.initials: S
authors.lastname: Sriwiriyajan
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. Electronic address: ibnuidris1@gmail.com.
authors.forename: Aman
authors.initials: A
authors.lastname: Tedasen
authors.affiliation: Molecular Medicine and Cancer Biology Research Unit, School of Allied Health Sciences and Public Health, Walailak University, Nakhon Si Thammarat 80161, Thailand. Electronic address: poonsit.hi@wu.ac.th.
authors.forename: Poonsit
authors.initials: P
authors.lastname: Hiransai
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. Electronic address: gpotchan@medicine.psu.ac.th.
authors.forename: Potchanapond
authors.initials: P
authors.lastname: Graidist
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D029222:Piper nigrum / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D042501:Angiogenic Proteins; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D008770:Methylnitrosourea
keywords: Anti-cancer; Breast cancer; MCF-7; Piper nigrum; ZR-75-1