title: Antitumor evaluation of two selected Pakistani plant extracts on human bone and breast cancer cell lines.
abstract: BACKGROUND
  The medicinal plants Vincetoxicum arnottianum (VSM), Berberis orthobotrys (BORM), Onosma hispida (OHRM and OHAM) and Caccinia macranthera (CMM) are used traditionally in Pakistan and around the world for the treatment of various diseases including cancer, dermal infections, uterine tumor, wounds etc. The present study focuses on the investigation of the selected Pakistani plants for their potential as anticancer agents on human bone and breast cancer cell lines in comparison with non-tumorigenic control cells.
  
  
  METHODS
  The antitumor evaluation was carried out on human bone (MG-63, Saos-2) and breast cancer cell lines (MCF-7, BT-20) in contrast to non-tumorigenic control cells (POB, MCF-12A) via cell viability measurements, cell cycle analysis, Annexin V/PI staining, microscopy based methods as well as migration/invasion determination, metabolic live cell monitoring and western blotting.
  
  
  RESULTS
  After the first initial screening of the plant extracts, two extracts (BORM, VSM) revealed the highest potential with regard to its antitumor activity. Both extracts caused a significant reduction of cell viability in the breast and bone cancer cells in a concentration dependent manner. The effect of VSM is achieved primarily by inducing a G2/M arrest in the cell cycle and the stabilization of the actin stress fibers leading to reduced cell motility. By contrast BORM's cytotoxic properties were caused through the lysosomal-mediated cell death pathway indicated by an upregulation of Bcl-2 expression.
  
  
  CONCLUSIONS
  The antitumor evaluation of certain medicinal plants presented in this study identified the methanolic root extract of Berberis orthobotrys and the methanolic extract of Vincetoxicum arnottianum as promising sources for exhibiting the antitumor activity. Therefore, the indigenous use of the herbal remedies for the treatment of cancer and cancer-related diseases has a scientific basis. Moreover, the present study provides a base for phytochemical investigation of the plant extracts.
authors.affiliation: Department of Pediatric Surgery, University Hospital Marburg, Baldingerstraße, Marburg, 35034, Germany. nadja.engel-lutz@gmx.de.|Department of Cell Biology, University Medical Center Rostock, Schillingallee 69, Rostock, 18057, Germany. nadja.engel-lutz@gmx.de.
authors.forename: Nadja
authors.initials: N
authors.lastname: Engel
authors.affiliation: Department of Chemistry, Karakoram International University, Gilgit-Baltistan, 15100, Pakistan.|Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, Rostock, 18059, Germany.
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Ali
authors.affiliation: Department of Cell Biology, University Medical Center Rostock, Schillingallee 69, Rostock, 18057, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Adamus
authors.affiliation: Medical Biology and Electron Microscopy Centre, University Medical Center Rostock, Strempelstraße 14, Rostock, 18057, Germany.|University of Education Vehari Campus, Punjab, Pakistan.
authors.forename: Marcus
authors.initials: M
authors.lastname: Frank
authors.affiliation: Department of Chemistry, Karakoram International University, Gilgit-Baltistan, 15100, Pakistan.
authors.forename: Akber
authors.initials: A
authors.lastname: Dad
authors.affiliation: Department of Chemistry, Karakoram International University, Gilgit-Baltistan, 15100, Pakistan.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Cell Biology, University Medical Center Rostock, Schillingallee 69, Rostock, 18057, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nebe
authors.affiliation: Medical Biology and Electron Microscopy Centre, University Medical Center Rostock, Strempelstraße 14, Rostock, 18057, Germany.|University of Education Vehari Campus, Punjab, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Atif
authors.affiliation: Department of Chemistry, Karakoram International University, Gilgit-Baltistan, 15100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.affiliation: Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, Rostock, 18059, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.affiliation: HEJ Research Institute of Chemistry, ICCBS, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Viqar Uddin
authors.initials: VU
authors.lastname: Ahmad
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001859:Bone Neoplasms; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D010154:Pakistan; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Actin cytoskeleton; Antitumor evaluation; Plant extracts; Traditional herbal remedies