title: Interaction of a standardized mistletoe (Viscum album) preparation with antitumor effects of Trastuzumab in vitro.
abstract: BACKGROUND
  Besides conventional anticancer therapy many breast cancer patients use complementary and alternative medicine (CAM) like the medicinal herb mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug interactions between CAM and conventional anticancer medications, in the present in vitro study we investigated the effect of a standardized mistletoe preparation on the action of Trastuzumab, a drug used for the treatment of Her-2 positive breast cancer.
  
  
  METHODS
  The Her-2 positive human breast carcinoma cell line SK-BR-3 was treated with Trastuzumab. Different doses of the drug were combined with Viscum album extract (VAE) in clinically relevant doses. Proliferation, apoptosis, cell cycle and the secretion of vascular endothelial growth factor (VEGF) were analyzed.
  
  
  RESULTS
  No inhibition of antitumor efficacy of Trastuzumab by VAE was detected. VAE and Trastuzumab, either alone or in combination, inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE induced apoptosis, which was not observed for Trastuzumab. Cells treated with Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M arrest. After application of the two drugs in combination both G0/G1 and G2/M arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and VAE at clinically relevant doses showed additive inhibitory effects on VEGF secretion.
  
  
  CONCLUSIONS
  VAE did not interfere with cytostatic effects of Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.
authors: Iscador AG, Arlesheim, Switzerland. u.weissenstein@hiscia.ch.
authors: U
authors: http://orcid.org/0000-0001-7739-7235
authors: U
authors: Weissenstein
authors: Iscador AG, Arlesheim, Switzerland.
authors: M
authors: M
authors: Kunz
authors: Iscador AG, Arlesheim, Switzerland.
authors: K
authors: K
authors: Urech
authors: Iscador AG, Arlesheim, Switzerland.
authors: U
authors: U
authors: Regueiro
authors: Iscador AG, Arlesheim, Switzerland.|Institute of Integrative Medicine, Witten/Herdecke University, Herdecke, Germany.
authors: S
authors: S
authors: Baumgartner
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D000068878:Trastuzumab / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D028182:Viscum album / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D000068878:Trastuzumab
keywords: Apoptosis; Cell cycle; Cytostasis; Drug interactions; Her-2; Herceptin; Iscador; Mistletoe (Viscum album L.); Trastuzumab; VEGF