PMID- 36386174
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221118
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Viscum album mother tinctures: Harvest conditions and host trees influence the 
      plant metabolome and the glycolytic pathway of breast cancer cells.
PG  - 1027931
LID - 10.3389/fphar.2022.1027931 [doi]
LID - 1027931
AB  - Viscum album is a semi-parasitic plant used for over one hundred years in 
      complementary cancer therapy. The main commercial drugs used in cancer patients' 
      treatment are derived from the aqueous V. album extracts, whose cytotoxic 
      potential is mostly attributed to the aqueous soluble antitumoral metabolites. On 
      the counterpart, ethanol solvents must be used to obtain V. album mother 
      tinctures. This methodology permits better solubilization of phenolic compounds, 
      among others, which present antitumoral bioactivity. Recently, the metabolomics 
      approach revealed the influence of the host tree on the V. album subspecies 
      differentiation. To increase the scientific information about the chemical 
      differences related to the host trees and to clarify the seasonal influences, in 
      this study, the metabolome of 50 V. album mother tinctures from three subspecies 
      (abietis, album, austriacum) and five host trees (Malus domestica, Quercus sp., 
      Ulmus carpinifolia, Pinus sylvestris, Abies alba) was evaluated using summer and 
      winter plant harvests. The in vitro cytotoxic activities were investigated in 
      breast cancer cells (MDA-MB-231) and immortalized normal human keratinocytes 
      (HaCaT). The summer V. album mother tinctures presented higher cytotoxic activity 
      than winter ones. Among the summer samples, those prepared with V. album subsp. 
      album were more cytotoxic than V. album subsp. abietis and subsp. V. album subsp. 
      austriacum. The V. album harvested from Quercus petraea and Abies alba inhibited 
      the key-glycolytic enzymes: hexokinase (HK), phosphofructokinase (PFK), pyruvate 
      kinase (PK). This activity was related to a reduction in glucose uptake and 
      lactate production, which were host-tree-time-dose-dependent. The untargeted 
      metabolomic approach was able to discriminate the mother tinctures according to 
      respective botanical classes and harvest season. A total of 188 metabolites were 
      annotated under positive and negative modes. Fourteen compounds were responsible 
      for the samples differentiation, and, to the best of our knowledge, eight were 
      described in the Viscum album species for the first time. Our study shows the 
      interruption of the Warburg effect as a novel antitumoral mechanism triggered by 
      V. album mother tinctures, which is related to their metabolite profile. These 
      results bring scientific evidence that encourages the use of V. album mother 
      tinctures as a natural product for cancer therapy.
CI  - Copyright (c) 2022 Melo, Ochioni, Zancan, Oliveira, Grazi, Garrett, Holandino and 
      Baumgartner.
FAU - Melo, Michelle Nonato de Oliveira
AU  - Melo MNO
AD  - Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
AD  - Metabolomics Laboratory, Chemistry Institute, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Ochioni, Alan Clavelland
AU  - Ochioni AC
AD  - Laboratorio de Oncobiologia Molecular (LabOMol), Faculty of Pharmacy, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Zancan, Patricia
AU  - Zancan P
AD  - Laboratorio de Oncobiologia Molecular (LabOMol), Faculty of Pharmacy, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Oliveira, Adriana Passos
AU  - Oliveira AP
AD  - Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Grazi, Mirio
AU  - Grazi M
AD  - Hiscia Institute, Society for Cancer Research, Arlesheim, Switzerland.
FAU - Garrett, Rafael
AU  - Garrett R
AD  - Metabolomics Laboratory, Chemistry Institute, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Holandino, Carla
AU  - Holandino C
AD  - Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
AD  - Hiscia Institute, Society for Cancer Research, Arlesheim, Switzerland.
FAU - Baumgartner, Stephan
AU  - Baumgartner S
AD  - Hiscia Institute, Society for Cancer Research, Arlesheim, Switzerland.
AD  - Institute of Integrative Medicine, University of Witten/Herdecke, Herdecke, 
      Germany.
AD  - Institute of Complementary and Integrative Medicine, University of Bern, Bern, 
      Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20221031
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9662615
OTO - NOTNLM
OT  - Viscum album
OT  - anticancer
OT  - glycolytic enzymes
OT  - in vitro
OT  - metabolome
OT  - mistletoe
OT  - multivariate analysis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/18 06:01
PMCR- 2022/10/31
CRDT- 2022/11/17 11:39
PHST- 2022/08/25 00:00 [received]
PHST- 2022/09/30 00:00 [accepted]
PHST- 2022/11/17 11:39 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/18 06:01 [medline]
PHST- 2022/10/31 00:00 [pmc-release]
AID - 1027931 [pii]
AID - 10.3389/fphar.2022.1027931 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Oct 31;13:1027931. doi: 10.3389/fphar.2022.1027931. 
      eCollection 2022.