Mistletoe extracts
Posted: 23 Mar 2023, 13:51
Viscum album mother tinctures: Harvest conditions and host trees influence the plant metabolome and the glycolytic pathway of breast cancer cells
Michelle Nonato de Oliveira Melo, Alan Clavelland Ochioni, Patricia Zancan, Adriana Passos Oliveira, Mirio Grazi, Rafael Garrett, Carla Holandino, and
Stephan Baumgartner
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-treetime-
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.
KEYWORDS
Viscum album, mistletoe, metabolome, multivariate analysis, glycolytic enzymes,
anticancer, in vitro
Michelle Nonato de Oliveira Melo, Alan Clavelland Ochioni, Patricia Zancan, Adriana Passos Oliveira, Mirio Grazi, Rafael Garrett, Carla Holandino, and
Stephan Baumgartner
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-treetime-
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.
KEYWORDS
Viscum album, mistletoe, metabolome, multivariate analysis, glycolytic enzymes,
anticancer, in vitro