Lichens Produce Anticancer compounds. How long before we see them used to treat cancer?
“Late in life I have come on fern.
Now lichens are due to have their turn.”
ROBERT FROST
Have you ever noticed the yellow lichens that grow on trees and rocks?
They’re quite a brilliant yellow and I see them in so many different places. The other day I was out for a walk around a local pond and saw some growing on the trees.
If you’ve been following my blog, you know I’m a big fan of lichens. I see lichens everywhere! On fence posts, rocks, trees, sidewalks, and especially when I’m hiking. If I see a really nice patch, I photograph them and often I forget to take the time to identify them.
But these yellow ones just called out to me to be identified!
So I took a close-up picture and when I got back home, I took out my favourite lichen book and there it was, Xanthoria parietina. There are lots of common names for it including Maritime Sunburst Lichen, Common Orange lichen, Yellow Scale, Stonebreaker, Stoneflower, and Shore lichen.
Photo taken by Rich Sobel
The species was first described by Carl Linnaeus in 1753, as Lichen parietinus. Aptly enough, the species name, parietina, means “on walls” so we can guess where he first collected it almost 5 centuries ago!
The book’s description provided some great anatomical details and taxonomic info but that’s about it. And it tells me I can find it on bark, wood and stone, common in coastal areas.
Origin of the word Lichen: There are 2 possibilities. It may derive from the Greek LEIKO ‐ to lick or lick up. This refers to how some species appear to “lap their tongues” all over the host. The second possibility is from Dioscorides. He thought they resembled the skin of afflicted people (“leprous, warts or eruption”). The French scientist Tournefort officially named them in 1700 AD.
How disappointing! There’s got to be more information about a lichen this beautiful!
Ok, I Google it and sure enough, this is one very interesting lichen!
First I found out a bit more about its ecology and distribution.
The species is found growing over both inland and maritime rocks between elevations of 5 to 283 m. It is known from Australia, Pacific Islands, Antarctica, Africa, Europe, South America, North and Central America, and Asia.
Then I came across a whole lot more information that discussed how traditional cultures have used it and other lichens as food and medicines over the millenia.
Next, I searched for scientific articles about it and found out it produces some very intriguing compounds. They include anthraquinones, xanthones, dibenzofurans, depsides and depsidones.
Ok, those names mean nothing to most of us! What’s so intriguing about those compounds?
Simple. Those classes of compounds are being tested for treating various infectious diseases and cancer.
Even more interesting is the fact that many of these compounds are only made by lichens. And to top it off, X. parietina is one of the primary lichens being investigated for producing them!
As a matter of fact, X. parietina is so ubiquitous and important that it was chosen by the Joint Genome Institute as the first lichen to sequence!
“Xanthoria parietina was chosen as a model organism to represent lichen-forming fungi because it has a wide distribution (being found in temperate and circumpolar regions worldwide), …and is one of the most commonly studied lichenized fungi….Genome analysis is anticipated to provide insights into the genetic basis of biological phenomena such as mutualistic symbiosis, adaptation to harsh environments, secondary metabolism, fungal sexuality, and control of growth rate in the lichenized habit.”
This is a lichen worth telling a story worth about!
In this article, you’ll learn a little bit about Xanthoria parietina and a few other lichens and how they are used as food and medicines in traditional cultures. That piqued the curiosity of modern researchers. They began to explore the medicinal properties of lichens, including X. parietina, and how they might be used to produce more effective drugs for treating cancer.
How Did Traditional Cultures Use Lichens?
Lichens as Food
Humans have been using lichens for a long time! There are over 15,000 different species of lichens and in some regions, they are quite abundant. So it’s not surprising that we have found ways to make use of them. We’ve used them to make perfumes, alcohol and dyes.
And just like deer and other animals, humans eat lichens.
Documented use of lichens in Europe started in the 15th and 16th centuries. Many of the ways they were employed were based on the early Greek “Doctrine of Signatures”. This doctrine suggested that “plants bearing parts that resembled human body-parts, animals, or other objects were thought to have useful relevance to those parts, animals or objects.”
Crops in Europe during the mid 18th century were badly affected by frosts and droughts that caused a famine. Because of their easy availability, cheapness and nutritive value people ate lichens to help keep themselves from starving.
Lichens as Medicines
In addition to their use as food, many traditional cultures have also used them as medicines to treat diseases and for their therapeutic values.
Some of the ways they are commonly used is as dressing for wounds, as a disinfectant, or to stop bleeding. They have also been applied directly to skin infections and sores to promote healing or reduce the pain.
For example, in Nepal the local inhabitants of different regions have a long tradition of using lichens among the lichenophilic communities residing in the eastern mountainous parts of Nepal. Although the different regions of Nepal have different names for lichens, the most common is Jhyauu, which means “brittle stuff”.
Nepalese use the lichen Heterodermia diademata (one of the many lichens also called shield lichens) against cuts and to heal wounds. Peoples in the Western region of Nepal use it to treat moles.
Heterodermia diademata shield lichen (left) and Usnea beard lichen (right)
Different regions of the world employ different lichen genera in their traditional medicines, with another genus, Usnea (also known as Old Man’s Beard or Beard Lichen), being the most widely used.
Other traditional societies in the temperate and arctic regions commonly used lichens for treating wounds, skin disorders, respiratory and digestive issues. They were also employed to treat obstetric and gynecological problems, and for urinary and sexually transmitted infections.
Less commonly, they have also been used to treat eye and foot problems and are found in smoking mixtures.
Remember X. parietina, the lichen that got me started down this path?
Because of its color (remember the Doctrine of Signatures?) X. parietina has been used against jaundice in traditional medicine since antiquity.
In Andalucia, Spain, it is commonly called Rompepiedrea (Stonebreaker) or Flor de piedra (Stoneflower) and is used as a painkiller.
The Andalucians prepare a decoction of the surface-contacting part of X. parietina with wine and use that to treat menstrual complaints. A decoction in water of the aerial parts of the plant is taken to treat kidney disorders and relieve toothaches and several other pains.
It is also one of the ingredients of a cough syrup they make. They combine it with carob and fig fruits, flowers and leaves of oregano, the pericarp of almonds, olive tree leaves and abundant sugar or honey.
Note: a decoction is what you get when you boil plant materials like stems, roots, bark or leaves and then discard the materials. A very crude extract.
It has also been used in Europe during the 18th and 19th centuries to treat jaundice, stop bleeding, replace quinine to treat malaria and for treating hepatitis.
So X. parietina was and continues to be used for a variety of traditional treatments and remedies.
Using Lichens to Treat Cancer
I mentioned above that all these traditional uses sparked interest in some modern researchers to investigate their medicinal properties more thoroughly.
What they initially found was that many of the lichens had antibiotic, antitumour, antifungal, and antiviral activity. They also inhibited some important enzymes and plant growth.
Recent developments in analytical techniques have allowed the identification of over 1000 lichen substances that included the anthraquinones, xanthones, dibenzofurans, depsides and depsidones I mentioned above.
Maybe the pharmaceutical or agricultural industries could put these to use?
An article published earlier this year by Zuzana Solárová and colleagues reviewed the most recent papers dealing with anticancer activities of lichen substances. They were particularly interested in their potential clinical use for cancer management.
The previous work used some of the compounds mentioned above to treat human cancer cell lines. When the cells were exposed to the lichen substances they were either killed or they stopped growing and failed to produce new cells.
And that brings us back to X. parietina and how they did these kinds of tests.
Basically, they collect the lichens in the field, then bring them back to the lab and extract the compounds from them.
When they did this with X. parietina, its extract inhibited the proliferation of MCF-7 and MDA-MB-231, two of the most commonly used breast cancer cell lines in breast cancer research laboratories.
It also stopped the cells from growing by inhibiting their cell cycle. And it caused increased expression of 2 proteins that are associated with increased cell death. It also decreased the levels of another protein, one that protects against cell death!
Growing just the fungal part
Ok, we need a quick refresher on some basic lichen biology to understand what happens next.
Lichens are not a single organism. Most often they are a combination of an algae and a fungus that mutually “agree” to team up and form a single organism.
Because the algal partner uses photosynthesis to generate energy for the lichen, it is often referred to in the lichen literature as the photobiont.
The fungal partner is called the mycobiont. “myco” comes from the Greek: μύκης (mukēs), meaning “fungus”. A “-biont” is a discrete living organism.
It turns out that you can isolate either the photo- or myco- bionts and grow them independent of each other.
One of the neat things about being able to grow just the algae or the fungus, is then you can vary the temperature, supply them with different kinds of nutrients, grow them in liquid culture or on solid media like agar.
When you do that, they respond by making different compounds and at different amounts. At first we didn’t know a lot about the biological activities of substances made by the separated bionts.
And our favourite lichen, X. parietina?
In a study conducted in Beata Guzow-Krzemińska’s laboratory, they looked at the anticancer activity of three common lichens, Caloplaca pusilla, Protoparmeliopsis muralis and X. parietina.
The Guzow-Krzemińska team isolated and grew just the fungal component (mycobiont) of these lichens on G-LBM media (See the image below). Then they ground them up and extracted them as I described above.
The three lichen mycobionts were incubated for 2 months on G-LBM media. Taken from the paper cited above.
When they grew the X. parietina fungus under two different culture nutrient conditions, they decreased the viability of HeLa cells or MCF-7 cancer cells. HeLa cells are derived from a cervical cancer patient and are one of the most famous cell lines used for cancer research.
Note: viability is the measure of the number of live cells vs dead cells in a cell culture. Wikipedia defines it as “the ability of a thing (a living organism, an artificial system, an idea, etc.) to maintain itself or recover its potentialities.“
When X. parietina mycobiont was grown on PDA and G-LBM it decreased the viability of MCF-7 and HeLa cell lines.
The C. pusilla mycobiont showed the highest potency in decreasing MCF-7, PC-3 (a cell line derived from prostate cancer) and HeLa cancer cells viability. It also showed greater amounts of cell death in HeLa, PC-3 and MCF-7 cell lines as they were treated with increasing concentrations of the C. pusilla extract.
Why was this work so important?
Back to basic lichen biology.
If you want to use lichens for treating a disease as prevalent as cancer, you’re going to need quite a bit of it. Again and again.
Have you ever watched a lichen grow? Don’t!
Ummm, they grow quite slowly. Like, if you took a picture of one this year and then came back and took it again the next year and the year after, you might not notice much difference in the size or shape of it.
That means that if you wanted to use any of these lichen compounds in significant amounts, you’d have to harvest a lot of lichens! And once they’re harvested, it would take years for them to grow back.
The beauty of being able to grow the lichen mycobiont in the lab is that you can experiment to find ways to speed up its growth by varying things like sugar and other chemical concentrations. So you can grow a lot pretty fast. Over and over and over again.
If you can do that, there’s no need to harvest them from the wild.
I like that! Very eco-friendly. 👏
You can also do breeding and mutation studies to select for strains that grow even better than the wild types and produce more of the chemicals you are interested in.
And that is what big pharmacological companies look for. Something they can easily manufacture in large batches to get lots of the chemical compound they want to use for making a drug or additive they can sell.
But before they invest the millions of dollars and years of time required, they want a little reassurance that what they are going to produce is going to work on people. And to know that, they have to do clinical trials.
While the lichens have produced some interesting anticancer candidates, I don’t know of any clinical studies that have been performed to see if they actually reduce or eliminate tumours in people.
That is the critical next step.
So let’s keep our eyes and ears open and if you hear of any clinical trials using lichen anticancer compounds, please let me know and I’ll do the same for you!
I hope you enjoyed the path this article took you down. We started with wanting to know a bit more about a pretty lichen and look where we ended up!
Possibly having new compounds in our arsenal to fight cancer.
That’s one of the things I love about science. You never know where the questions you ask and the answers you get will take you!
Until next time,
Rich
For Additional Reading: The main sources I used to gather the information.
- Lichens Used in Traditional Medicine, Stuart D. Crawford, from his chapter in the book, “Lichen Secondary Metabolites” pp 27-80, Dec 2014, and personal communication.
- Anticancer Potential of Lichens’ Secondary Metabolites, Zuzana Solárová,1 Alena Liskova, Marek Samec, Peter Kubatka, Dietrich Büsselberg, and Peter Solár, Biomolecules. 2020 Jan; 10(1): 87
- Antibacterial and anticancer activities of acetone extracts from in vitro cultured lichen-forming fungi, Agnieszka Felczykowska, Alicja Pastuszak-Skrzypczak, Anna Pawlik, Krystyna Bogucka, Anna Herman-Antosiewicz, and Beata Guzow-Krzemińska, BMC Complement Altern Med. 2017; 17: 300.
- Indigenous knowledge and use of lichens by the lichenophilic communities of the Nepal Himalaya, Shiva Devkota, Ram Prasad Chaudhary, Silke Werth, and Christoph Scheidegger, J Ethnobiol Ethnomed. 2017; 13: 15. Published online 2017 Feb 21.
- Biopharmaceutical potential of lichens, Vasudeo P. Zambare & Lew P. Christopher, Pharmaceutical Biology, 50:6, 778-798, 2012
- Medicinal Lichens, by Robert Rogers
- Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoriaparietina and Its Secondary Metabolite Parietin, Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S., Conte B., Paoli L., De Ruberto F., Molinari A., et al.. IJMS; 16:7861–7875, 2015
- Three Lichens Used in Popular Medicine in Eastern Andalucia (Spain), Gonzalez-Tejero, M. R., M. J. Martinez-Lirola, M. Casares-Porcel, and J. Molero-Mesa, Economic Botany 49(1) 96-98. 1995.
- Have lichenized fungi delivered promising anticancer small molecules? Alessio Cimmino, Pier Luigi Nimis, Marco Masi, Laura De Gara, Willem A. L. van Otterlo, Robert Kiss, Antonio Evidente, Florence Lefranc, Phytochem Rev. 2019, 18:1–36.
