VISCUM ALBUM ETHANOLIC EXTRACTS: 2D AND 3D CELLULAR ANTITUMOR ACTIVITY AND GLYCOLYTIC PATHWAY MECHANISMS

Vol 1, 2020 - 131618
DR - Doctoral Student
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Abstract

INTRODUCTION AND OBJECTIVES: In vitro and clinical antitumor efficacy of Viscum album is mainly attributed to the aqueous preparations. However, Viscum album ethanolic extracts (VAE), as mother tinctures prepared from different host trees, have demonstrated antiproliferative activity in 2D and 3D cellular models. MATERIAL AND METHODS: Viscum album subspecies album, austriacum, and abietis were harvested from five different host trees to prepare their respective mother tinctures. Phytochemical analyses were performed by thin layer chromatography, high-performance liquid chromatography and liquid chromatography-high resolution mass spectrometry. The antitumor activity using 2D cell models was evaluated by WST-1 and Annexin V-7AAD in Yoshida, Molt-4 (tumor cell lines), and NIH/3T3 (non-tumor cells). The glycolytic pathway analysis in 2D model investigated cell death mechanism, MTT and crystal violet evaluated the effect of the mother tinctures in human breast adenocarcinoma (MDA-MB-231) 3D cell line model. RESULTS AND CONCLUSIONS: Phenolic acids, flavonoids and lignans were the main chemical classes identified in VAE. V. album ssp. abietis from Abies alba (VAA) was the most effective to induce 2D in vitro cellular effects. Necrotic damage, which was host tree-, time- and dose- dependent, was observed by colorimetric and FACS methodologies, with different selectivity to non-tumor and tumor cell lines. The MDA-MB-231 glycolytic pathway in the 2D model showed a decrease in glucose consumption and extracellular lactate production. PFK (6-phosphofructo-1-kinase) and PK (Pyruvate kinase) activities were inhibited by VAA and VAQ (V. album ssp. album growing on Quercus sp.) after 48h of incubation. Regarding to 3D cell models and seasonal aspects, VAA and VAQ from summer harvests induced higher cytotoxic damage than winter preparations, with 49% and 42% tumor viability reduction, respectively. VAE presented antitumor activity in both 2D and 3D models. The glycolytic pathway (PFK and PK enzymes) should be an important target and needs further investigation.

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Institutions
  • 1 Multidisciplinary Laboratory of Pharmaceutical Sciences / Pharmacy College / Federal University of Rio de Janeiro
  • 2 Metabolomic Laboratory (LabMeta/LADETEC), Chemistry College, Federal University of Rio de Janeiro
  • 3 Molecular Oncobiology Laboratory (LabOMol) / Pharmacy College / Federal University of Rio de Janeiro
  • 4 Hiscia / Society for Cancer Research
Track
  • Drugs and/or Natural Products Therapy
Keywords
Viscum album
antitumor
ethanoli extract
glycolysis