Taraxacum Officinale and Cancer
Food

Author: Alfredo Macheda
Date: 26/09/2012

Description

TARAXACUM OFFICINALE AND CANCER

THE PLANT


Taraxacum officinale, also called dandelion (in italian tarassaco o dente di leone) is a flowering herbaceous perennial plant of the family of Asteraceae. It is extremely widespread in every areas of the world characterized by a temperate climate and it grows up to 2000 m altitude. It has strong roots and simple leaves with sharp edge. The flower is equipped with the characteristic pappus, a structure made by bristles that, working as a parachute, promotes the diffusion of the seeds by the wind.

Taraxacum is rich in biological active substances. There are a lot of vitamins (B1, B2, C, E), linoleic and linolenic acids, terpenes and flavonoids like apigenin and luteolin.

Taraxacum has been used for a long time not only as healthy food, but as healing herb too; in fact, Chinese traditional medicine assigns to this plant several medicinal properties. Some of this characteristic:

  • Diuretic action
  • Cholagogue action, that prevents the formation of gallstones
  • Anti-infective and anti-cancer action

Without a dubt, one of the most interesting substance contained in Taraxacum is luteolin.
Luteolin (3′,4′,5,7-tetrahydroxyflavone) belongs to a big family of substances called flavonoids. They are polyphenolics compounds, secondary metabolites of the plants, and protect plants against micro-organisms, UV radiations and insects. Flavonoids are situated especially in flowers and leaves, where they act as coloured pigments. Like other flavonoids, luteolin exhibits anti-oxidant activity against ROS. This ability derives from its structure: 3′, 4′ hydroxylation, the presence of a double bond between carbons 2 and 3, and a carbonyl group on carbon 4; the hydrogen atom from an aromatic hydroxyl group can be donated to free radicals.

Luteolin acts as anti-oxidant in several ways:

  • It can function as a ROS scavenger through its own oxidation
  • It can inhibit ROS-generating oxidases, like xanthine oxidase
  • It can active endogenous antioxidants such as glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)
  • It can inhibit cyclooxygenase and lipoxygenase, with obvious anti-inflammatory effect
  • It can chelate metals involved in ROS formation

Recent studies expose that luteolin really has a mighty anti-cancer ability, due to its action on a remarkable amount of cellular enzymes. Even more important, luteolin shows a specific cytotoxicity, limited to cancer cells.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615542/

Some of its targets:

Probably, the last aspect is the most important in the role of luteolin-induced apoptosis.
To introduce the relationship between luteolin and inhibition of Nf-kb pathway is necessary to say that, in addition to its well known anti-oxidant activity, luteolin has a pro-oxidant activity. The reason is not completely understood: it is supposed that the cellular microenvironment, and concentration of metal, plays a central role. In fact, it was observed that with low Fe ion concentrations (< 50 μM), luteolin behaves as an antioxidant while high Fe concentrations (>100 μM) induce luteolin's pro-oxidative effect. It was reported that luteolin can origin a large amount of superoxide anion, through its own oxidation caused by interaction with metal; in other cases, it was observed that the phenol rings of flavonoids can be metabolized by enzymes peroxidase to form pro-oxidant phenoxyl radicals sufficiently reactive to co-oxidize glutathione (GSH) or nicotinamide-adenine hydrogen (NADH), accompanied by extensive oxygen uptake and ROS formation. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615542/

The ability to create ROS is fundamental to explain how luteolin interfere with Nf-kb. In fact, Nf-kb antagonizes programmed cell death induced by the pro-inflammatory cytokine TNFα: in a normal cell, this pathway is usually involved in inflammation, lymphopoiesis and osteogenesis; in a cancer cell, this pathway is involved in tumorigenesis and radio- and chemoresistance. After its release by the departure of IKBα (phosphorylated by IKK and the destroyed) Nf-kb moves to the nucleus and activates genes whose products participate in inflammatory reaction, cell proliferation and survival and, most of all, resistance to apoptosis. Nf-kb suppresses the JNK pathway (generally involved in pro-apoptotic stimulation) through the activation of select downstream targets such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase, Gadd45beta/Myd118. This last one enzyme directly binds and inhibits JNK with a not completely understood way. Furthermore, Nf-kb lowers the accumulation of ROS inside the mitochondria, increasing the production of the heavy chains of ferritin, the human iron-storage protein, and MnSOD. It seems clear that an irregular Nf-kb pathway encourages cancer progression and, on the other hand, that its suppression improves TNFα-induced anti-cancer action.

http://www.ncbi.nlm.nih.gov/pubmed/15611622
http://www.ncbi.nlm.nih.gov/pubmed/16267788
http://www.ncbi.nlm.nih.gov/pubmed/14743220

It was observed that luteolin somministration sensitizes lung and colorectal cancer cells to the TNFα-induced apoptosis through the inhibition of the Nf-kb pathway. In particular:

  • it was demonstrated that luteolin promotes ROS formation and their accumulation inside the mitochondria, since the suppression of MnSOD
  • the somministration of ROS-scavengers cancels luteolin action and its synergy with JNK system

This indicates that pro-oxidant ability of luteolin and consequently the production of ROS is important to antagonize and inhibit Nf-kb action, to improve JNK cascade and TNFα-induced pathway.
http://www.ncbi.nlm.nih.gov/pubmed/17296806

CONCLUSIONS

It was demonstrated that luteolin has a wide variety of benefits. Although the mechanism is not yet completely understood, its antitumor properties are attributed in part to its pro-oxidant abilities. Furthermore, it is important to discover its selective cytotoxicity: it is supposed that it may come from the activation, in tumor cells, of a metabolic pathways absent in normal cells. Until now luteolin has not demonstrated side effects, except a case of worsening colitis in transgenic mice. If we could use this flavonoid in the war against cancer, we may get cheap, effective, side effects free and potentially active against tumors chemotherapy resistant, such as melanoma.
http://www.ncbi.nlm.nih.gov/pubmed/21234313
http://www.ncbi.nlm.nih.gov/pubmed?term=luteolin%20mice%20colitis

Sources used for the images:
http://terre-alte.blogspot.it/2012/04/insalata-di-tarassaco-e-fiori.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615542/

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