The Many Ways Bee Propolis Can Fight Many Cancers
Bee propolis and its marked anti-cancer effects, let alone vast array of other incredible health benefits, is the latest example I’ve found of a product of God’s creation providing scientifically backed astounding results that you’ve probably never heard about mainly because it wouldn’t serve the medical industrial complex if you had. Indeed, at the time of this writing, PubMed has a whopping 2,227 studies on propolis itself and 299 studies on propolis and cancer. The smaller DOAJ has 598 and 36, respectively. And just to spell out what this high number of studies performed means, the stuff works. If there had been nine studies performed showing propolis had little to no effect on the ailment being studied, the tenth guy would have moved onto something with better promise. But that’s clearly not the case here. Scientists keep on getting positive results, thousands of them now, so they keep on performing studies from different angles. At the end, they’ll usually mention something along the lines of “these results are so good, work is underway to try and synthesize this substance to turn it into a drug.” If they eventually come out with a sorry excuse for the real thing, THEN you’ll hear about it all over TV… You just won’t hear the word propolis itself used.
Wait, What is Bee Propolis Again?
So what is bee propolis? Great question! I didn’t know either until a few weeks ago. By now we’ve all heard that (raw, organic, local) honey has a host of health benefits outside of tasting delicious. Turns out the little guys actually make a few substances highly beneficial to human health in going about their daily business (yet another reason Monsanto and their kind need to be stopped from killing the rest of them!). Propolis is made when bees collect resin from conifer (cone producing) trees and plants to bring back to the hive. [xxii] The resin is blended with pollen and wax flakes and the mixture is basically used for construction material. It’s good for everything from patching holes to sealing cracks and even building new panels. In addition, due to its antiseptic properties, bees will coat the entire hive with propolis to serve as a barrier from invaders, killing pathogens and embalming predators, which explains why the word comes from a Greek term for “in defense of the city.” [xiii]
As noted on aloe arbrorescens in a previous article, propolis has been used for thousands of years by various cultures for various medicinal purposes, while modern day science is just starting to catch up. [xxii] Aside from its anti-cancer properties, which is the focus of this article, propolis and its various chemical compounds (mainly flavonoids and phenolic acids) have significant anti-microbial action, heal burns, prevent dental cavities and can even treat gingivitis, treat parasites, remove warts, AND even beat out a popular herpes drug in a study for treating symptoms!! [xiii] Not bad for something made by bees right?
A Propolis Study for Just About Every Cancer
Although I tend to use more neuroblastoma studies as a first priority in research for my son Ryder, a 2015 review of all studies to date on propolis and cancer found that it does just about everything you’d want an anti-cancer agent to do to just about every type of cancer. The author states “Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers.” Apparently, there’s so much out there she couldn’t even get to all of it as she didn’t mention nerve cancer, which is how I found out about it in the first place! The same review found that propolis can induce apoptosis (cell “suicide”), prevent metastasis (spreading to other organs) and angiogenesis (tumors forming their own blood supply), cause cell cycle arrest (prevents cells from multiplying), and even moderate deleterious side effects from chemotherapy!! [xiii] We love therapies such as this that come with a lot of bang for the buck (see our vitamin C article for another one) so we’re very excited to have it in our protocol.
Digging in a little deeper, the reason propolis serves so many functions is that it is composed of so many different chemical compounds. Each tree or plant the bee gathers resin from brings something unique to the table. As you might guess, this means that propolis from different regions can contain entirely different compounds. For instance, the most highly studied compound in propolis coming out of New Zealand, Europe, and some parts of Brazil along with the far-east is caffeic acid phenethyl ester (CAPE), whereas, in red or green propolis from Brazil, the best known ingredient is artepillin C (ARC). Luckily, from what I gather, it seems that even though the compounds are different, they still add up to produce roughly the same result. CAPE and ARC, for example, both block the oncogenic PAK1 signaling (I’ll get to what this means later). [xix]
Combine with Vitamin A for Best Results!
I initially found out about propolis and its anticancer benefits while pouring through neuroblastoma studies on DOAJ after our son’s last questionable MRI result. One of the most interesting studies confirmed the authors’ previous findings that combining 5-lipoxygenase (LOX) and cyclooxygenase-2 (COX) inhibitors with all-trans retinoic acid (ATRA) significantly enhanced differentiation in two different neuroblastoma cell lines. [vi] Now in English: The acne drugs Accutane and Retin-A (synthetic retinoids) have worked their way into many standard conventional protocols for neuroblastoma and other cancers as they have found high doses of retinoids (compounds that make up vitamin A) to be effective in getting the cancer cells to differentiate, which basically means to turn normal, and they’re now finding in certain cancers that these 5-LOX and COX-2 (particular enzymes) inhibitors in combination with retinoic acid produce even better results.
Fortunately, Ryder already gets high amounts of retinoids from a few sources. The best natural source of retinoids is from liver, which he gets in the form of cod liver oil. Grass fed butter and pastured egg yolks are also delicious sources of retinoids which he often enjoys. Carotenoids such as Beta-Carotene from carrots are also converted by the body into retinoids. Although the conversion isn’t entirely efficient, Ryder gets plenty of carrot juice and carrot juice powder as well as there are many studies to be found on beta-carotene itself fighting neuroblastoma stem cells and several other cancers (Note: Unfortunately just searching beta-carotene and cancer now yields page after page of articles about a flawed study that got over hyped suggesting the beta-carotene can increase lung cancer risk in smokers. Search specific cancer types to avoid this), along with the well documented success of The Gerson Therapy in which carrot juice is the centerpiece. Lastly, red palm oil actually has a higher concentration of carotenoids than even carrot juice does, and as we make sure all of us are taking in plenty of healthy fats, he gets frequent spoonfuls of that as well.
The study had used a drug as well for inhibiting COX-2, so I simply searched in “natural COX-2 inhibitors” and found an article showing that several flavonoids (compounds that come from plants) along with omega-3 fatty acids have been shown to reduce COX-2. [ii] Turns out we already had our bases covered here too. Ryder gets the omega-3 from his Budwig diet breakfast and our rotating cast of fish oils, the flavonoids curcumin, resveratrol, and quercetin he gets in LifeOne and Calibr8, and genistein from Haelan 951 (you can see everything Ryder takes on our supplements page).
For inhibiting LOX-2, the researchers had used a substance called caffeic acid. When I looked into caffeic acid, I found that it’s found to a small degree in apples (which on a side note is just a little more validation Max Gerson was way ahead of his time), but one of its highest concentrations are found in… Bee propolis!
Propolis Treats Neurofibromatosis and In Turn Many Childhood and Adult Cancers
Doing a deep dive into propolis shows that this beneficial combination with retinoic acid is only the start of how it can fight neuroblastoma, along with most other childhood and adult cancers. As Samuel L. Jackson said in Jurassic Park when they’re about to shut power down to the whole island which for some reason just came back to me all these years later, “hold on to your butts!”
Propolis is well known for treating neurofibromatosis, a cancer of the nervous system similar to neuroblastoma. Neurofibromatosis (NF) is a family of genetic diseases which are caused by dysfunction of either NF1 gene or NF2 gene, which can get a little confusing because researchers will then call one disease neurofibromatosis type one and the other type two but then use the same abbreviations, NF1 & NF2 to describe the disease itself. Dysfunctions in the NF1 or NF2 gene can lead to a rise in the oncogenic (leading to tumor formation) kinase (enzyme that performs certain tasks) PAK1. Both types of neurofibromatosis require PAK1. [xvi] In addition, the NF1 gene also makes a tumor suppressor protein called neurofibromin which can be found in many types of cells, especially nerve cells. Mutations or dysfunctions in NF1 therefore create ineffective neurofibromin which can also lead to tumor formation. [xx]
So what does neurofibromatosis have to do with neuroblastoma and other childhood and adult cancers? A LOT. One study found that “four out of ten human neuroblastoma lines express little or no neurofibromin and that two of these lines show evidence of NF1 mutations, providing further proof that NF1 mutations occur in tumours that are not commonly found in NF1 patients.” [xii] Another found that low levels of NF1 (the gene) have extremely poor outcomes, and again that NF1 mutations are found in neuroblastomas. [xi]
From The Oncologist: “The oncologist will see NF1 patients referred for treatment of malignancy, and should be alert to the possibility of undiagnosed NF1 among patients with cancer… Gliomas, particularly pilocytic astrocytomas of the optic nerve, and leukemias, are seen with increased frequency in the NF1 population.” The same journal found that 15% of NF1 patients had signs of an optic glioma. [xv] The book Merritts Neurology adds neuroblastoma, Wilms tumor, pheochromocytoma, and sarcomas among others to the list. [xviii]
So what I’m reading from the studies mentioned in the last couple paragraphs is that patients with many different types of cancers could have actually had neurofibromatosis which in a sense led to their main cancer. Or, even without a full-blown diagnosable case of neurofibromatosis, it sounds like many cancers could actually share similar mechanisms to NF that contribute to their development. Either way, based on this knowledge and what you’re about to learn in the next paragraph, looking at some of the triggers of NF and how to address them seems to be prudent for most cancer types.
Block the PAK1, Block the Cancer
Back to caffeic acid (CAPE). Turns out it’s an extremely effective PAK1 blocker! [viii] In 2008, researchers found CAPE to COMPLETELY suppress the growth of an NF1 related tumor and cause an almost complete regression of an NF2 tumor (there are several types of tumors within the broader NF1 & NF2 categories). As I said above, researchers then ran studies on Artepillin C (ARC) in Brazilian green propolis and found it to be equally as effective in suppressing NF tumors. [xix]
Two studies I read stated that PAK1-dependent solid cancers altogether represent more than 70% of all human cancers. [xvi], [xix] So it sounds like blocking PAK1 would probably be a good idea for most people battling cancer… Has your oncologist mentioned this to you yet? I would imagine not as I found articles as recent as April 2014 stating that no FDA approved synthetic PAK1 blockers are even on the market, and I certainly can’t find any out today (although it looks like curcumin has this property to some extent as well by the way). [xvii] I should note as well that even though this statement deals with solid cancers, as mentioned above, there have been many successful propolis studies on leukemia and other cancers of the blood as well.
Aside from blocking PAK1, the ways I found in which propolis fights neuroblastoma, and following the trend here many other cancers as well, are almost too many to list out. For instance, one of the studies I mentioned above dealing with NF1 mutations in neuroblastoma found that loss of NF1 results in increased MEK signaling, which is a protein that when activated can lead to cell growth and survival. [xi] Sure enough, I quickly found another study saying that caffeic acid indeed inhibits MEK [x]. Targeting MEK has also shown success in a number of clinical trials for various cancers including melanoma, colorectal, multiple myeloma, breast, and pancreatic. [xv]
Propolis Even Fights Cancer Stem Cells!!
Hopefully by now we’ve all heard of cancer stem cells (CSC), the ones that have the ability to metastasize and are what cause relapses due to their resistance to chemo. In a study titled “Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells,” researchers found several compounds in Cuban propolis with “considerable anti-iCSC activity.” [vii] Here’s another for good measure showing compounds in Caribbean propolis targeting CSCs in neuroblastoma along with breast and prostate cancer, and again markedly disrupting MEK signaling to boot! [i]
Another study on p-Coumaric acid (found in propolis of certain regions) showed over 80% of neuroblastoma cells exposed to the compound were stimulated to apoptosis after being damaged so badly by the reactive oxygen species that was produced as a result, and went on to describe the cells’ membranes literally dissipating after exposure! [xix]
Propolis and Epigenetics
Perhaps the most exciting aspect to propolis pertaining to all cancers is its ability to work epigenetically in a positive way. Histone deacetylases are enzymes that can literally switch off entire regions of DNA, including tumor suppressor genes, which is what often contributes very heavily to uncontrolled cell growth in most cancers. Propolis has been shown to inhibit these enzymes and actually restore lost DNA function, thereby regaining cell’s ability to regulate their growth! [xxii] And I was even able to find a study linking this mechanism in particular to effectiveness against neuroblastoma cells as well. [xxi]
More Propolis Cancer Studies
Just in case you were starting to think propolis was only good for cancers that start with “neuro,” here’s some more quick studies on more ways propolis fights various childhood and adult cancers (also remember the review I mentioned at the start [xiii]): Leukemia Research found that propolis inhibited telomerase expression by 93% in lymphoblastic leukemia cells, a key factor in induction of apoptosis. [ix] Cell and Bioscience found that pinocembrin (found in Brazilian red propolis and New Zealand propolis among others) significantly suppressed invasion and migration abilities of retinoblastoma cells, among other means of control. [xxiii] Journal of Radiation Research showed that after three days of treatment with CAPE (NZ propolis and Brazilian brown), 67% of lung cancer cells had been destroyed. This next one is probably a good one to leave you with… Bioorganic and Medical Chemistry found that in a “nutritionally starved condition,” 100% of pancreatic cancer cells were killed by Brazilian red propolis… [iii] That sounds pretty good, right?
Studied out yet? I know I am, and believe it or not this article barely scratches the surface of what’s out there. Again although I was primarily digging up articles from a neuroblastoma perspective, I was amazed that propolis has been shown to work MANY different ways on MANY types of cancer. Seeing what’s out there for the type you might be dealing with is as easy as hopping on PubMed or DOAJ, or any regular internet search engine for that matter, and searching the specific type in combination with propolis and seeing what comes up. Bear in mind though, that even if there hasn’t been anything studied on your specific combination, it could very well be simply that no one’s gotten around to doing the study yet, and that what’s effective against one type of cancer is more often than not effective against another.
The Propolis We Use and How We Use It
Far and away the best brand for bee propolis out there is NaturaNectar. The company uses a proprietary water extraction method as opposed to ethanol or CO2 used by most others out there. There are a few huge advantages to doing it this way. The result is a nice powder in a capsule as opposed to a sticky liquid preserved in alcohol or propylene glycol, neither of which we were very excited about giving our son on a daily basis. Should you need to mix it into liquid, the powder has a slightly sweet taste and mixes fairly easily as opposed to the pungent and sticky liquid formulas. This extraction method removes ALL impurities instead of leaving in little goodies such as bee poo. Plus, since the company’s products revolve solely around propolis they are a wealth of knowledge and are on the forefront of emerging research into all the health benefits propolis has to offer.
What excites me most about NaturaNectar is their “Ultimate” product. In going through all of these studies it became very apparent that in order to realize the benefits from all of the compounds being researched one would need to be taking propolis from several different regions to get them all. Ultimate has three different regions’ propolis in one capsule. Not only does it include both of the most studied compounds, CAPE and Artepillin C, but also virtually every other compound I found being researched as well.
NOTE: My Kid Cures Cancer readers will get 25% off anything on the NaturaNectar site by entering MKCC into the coupon code box at checkout!!
As the study I mentioned showed a synergistic effect with retinoids, Ryder takes it right along with his carrot juice and a big scoop of palm oil. Since he is not old enough to take capsules, we mix it along with a few of his other supplements right in with the juice. A couple tips if you need to do the same for a child or anyone on a feeding tube. Add in a dash of MCT oil. It will keep the propolis from clumping together and healthy fats tend to help with absorption of nutrients. If you don’t already have one, get yourself a cheap little milk frother for making these mixtures. Finally if you’re using a feeding tube, you may end up needing to run everything through a sieve first. We always let everything soak in the juice to extract the nutrients and also worked everything through with a spoon to keep the nutrient loss to a minimum.
Whew… Now get out there and bee healthy! Sorry, I couldn’t resist :-). But please, on a serious note, take a look at some of these studies on propolis and cancer for yourself. You won’t bee disappointed!
Please note: Many links on this site, especially those to Amazon, are affiliate links. Should you click on these links and purchase something, the price is no different for you and we earn a small commission. Thank you for your support!
Disclaimer: The statements made here have not been approved by the Food and Drug Administration. These statements are not intended to diagnose, treat or cure or prevent any disease. This notice is required by the Federal Food, Drug and Cosmetic Act.
[i] Acikelli, Ali Haydar, Sebastian Gustmann, Walter Bardenheuer, Jacqueline Klein, Ulrike Dembinski, Bastian Kohl, King Tou Yip, Ali Nazif, Raphael Stoll, Dirk Strumberg, and David Díaz-Carballo. “Flavonoids Isolated from Caribbean Propolis Show Cytotoxic Activity in Human Cancer Cell Lines.” Int. Journal of Clinical Pharmacology and Therapeutics CP 51.01 (2013): 51-53. Cesar. Web. 16 Feb. 2016. <https://www.cesar.or.at/download/files/%7BCBC69BEF-1E61-4502-A422-CB9BA6CC78BB%7D/JT_2012_EA_06_Acikelli.pdf>.
[ii] Almada, Anthony. “Natural COX-2 Inhibitors: The Future of Pain Relief.” Chiro. N.p., 2000. Web. 16 Feb. 2016. <http://www.chiro.org/nutrition/FULL/Natural_COX-2_Inhibitors.shtml>.
[iii] Awale, S. “Constituents of Brazilian Red Propolis and Their Preferential Cytotoxic Activity against Human Pancreatic PANC-1 Cancer Cell Line in Nutrient-deprived Condition.” Bioorganic & Medicinal Chemistry 16.1 (2008): 181-89. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/17950610>.
[iv] Chen, Chia-Nan, Chia-Li Wu, and Jen-Kun Lin. “Propolin C from Propolis Induces Apoptosis through Activating Caspases, Bid and Cytochrome C Release in Human Melanoma Cells.” Biochemical Pharmacology 67.1 (2004): 53-66. Web. 16 Feb. 2016. <http://www.mundialsiglo21.com/novedades/Propolin%20C.pdf>.
[v] Chen, Kun-Shiang. “Pinocembrin Suppresses TGF-?1-induced Epithelial-mesenchymal Transition and Metastasis of Human Y-79 Retinoblastoma Cells through Inactivating ?v?3 Integrin/FAK/p38? Signaling Pathway.” Cell & Bioscience 4.41 (2014): n. pag. BioMed Central. 12 Aug. 2014. Web. 16 Feb. 2016. <http://cellandbioscience.biomedcentral.com/articles/10.1186/2045-3701-4-41>.
[vi] Chlapek, Petr. “Enhancement of ATRA-induced Differentiation of Neuroblastoma Cells with LOX/COX Inhibitors: An Expression Profiling Study.” Journal of Experimental & Clinical Cancer Research 29.45 (2010): n. pag. BioMed Central. 11 May 2010. Web. 16 Feb. 2016. <http://jeccr.biomedcentral.com/articles/10.1186/1756-9966-29-45>.
[vii] Díaz-Carballo, D. “Identification of Compounds That Selectively Target Highly Chemotherapy Refractory Neuroblastoma Cancer Stem Cells.” International Journal of Clinical Pharmacology and Therapeutics 52.9 (2014): 787-801. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/24902844>.
[viii] Demestre, M. “CAPE (caffeic Acid Phenethyl Ester)-based Propolis Extract (Bio 30) Suppresses the Growth of Human Neurofibromatosis (NF) Tumor Xenografts in Mice.” Phytotherapy Research 23.2 (2009): 236-30. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/18726924>.
[ix] Gunduz, Cumhur. “Evaluation of Manisa Propolis Effect on Leukemia Cell Line by Telomerase Activity.” Leukemia Research 29.11 (2005): 1343-346. LR Journal. Web. 16 Feb. 2016. <http://www.lrjournal.com/article/S0145-2126(05)00177-3/abstract>.
[x] Han, Honghui. “CADPE Inhibits PMA-Stimulated Gastric Carcinoma Cell Invasion and Matrix Metalloproteinase-9 Expression by FAK/MEK/ERK–Mediated AP-1 Activation.” Molecular Cancer Research (n.d.): n. pag. American Association for Cancer Research, 2010. Web. 16 Feb. 2016. <http://mcr.aacrjournals.org/content/8/11/1477.full>.
[xi] Hölzel, M. “NF1 Is a Tumor Suppressor in Neuroblastoma That Determines Retinoic Acid Response and Disease Outcome.” Cell 142.2 (2010): 218-29. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/20655465>.
[xii] The, I. “Neurofibromatosis Type 1 Gene Mutations in Neuroblastoma.” Nature Genetics 3.1 (1993): 62-66. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/8490657>.
[xiii] Ishiai, Shinobu. “Histone Deacetylase Inhibitory Effect of Brazilian Propolis and Its Association with the Antitumor Effect in Neuro2a Cells.” Food Science & Nutrition 2.5 (2014): 565-70. Wiley Online Library. Web. 16 Feb. 2016. <http://onlinelibrary.wiley.com/doi/10.1002/fsn3.131/full>.
[xiv] King, Margie. “7 Health Benefits of Bee Propolis.” Green Med Info. N.p., 26 Apr. 2015. Web. 16 Feb. 2016.
[xv] Korf, Bruce R., MD, PHD. “Malignancy in Neurofibromatosis Type 1.” The Oncologist (2000): n. pag. Malignancy in Neurofibromatosis Type 1. AlphaMed Press. Web. 16 Feb. 2016. <http://theoncologist.alphamedpress.org/content/5/6/477.full>.
[xvi] Maruta, H. “Effective Neurofibromatosis Therapeutics Blocking the Oncogenic Kinase PAK1.” Drug Discoveries & Therapeutics 5.6 (2011): 266-78. US National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/22466437>.
[xvii] Maruta, Hiroshi. “Herbal Therapeutics That Block the Oncogenic Kinase PAK1: A Practical Approach towards PAK1-dependent Diseases and Longevity.” Phytotherapy Research 28.5 (2014): n. pag. ResearchGate. Web. 16 Feb. 2016. <https://www.researchgate.net/publication/255952711_Herbal_Therapeutics_that_Block_the_Oncogenic_Kinase_PAK1_A_Practical_Approach_towards_PAK1-dependent_Diseases_and_Longevity>.
[xviii] Merritt, Hiram Houston, Lewis P.. Rowland, Elan D.. Louis, and Stephan A.. Mayer. “Neurocutaneous Syndromes.” Merritt’s Neurology. Philadelphia: Wolters Kluwer, 2016. N. pag. Print.
[xix] Messerli, SM. “Artepillin C (ARC) in Brazilian Green Propolis Selectively Blocks Oncogenic PAK1 Signaling and Suppresses the Growth of NF Tumors in Mice.” Phytotherapy Research 23.3 (2009): 423-27. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 16 Feb. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/19003952>.
[xx] “Neurofibromatosis Type 1.” Genetics Home Reference. U.S. National Library of Medicine, June 2012. Web. 16 Feb. 2016. <http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1>.
[xxi] Patel, Seema. “Emerging Adjuvant Therapy for Cancer: Propolis and Its Constituents.” Journal of Dietary Supplements 13.3 (2016): 245-68. Taylor & Francis. Taylor & Francis Group. Web. 16 Feb. 2016. <http://www.tandfonline.com/doi/full/10.3109/19390211.2015.1008614>.
[xxii] Roumeliotou, Eleni. “Extreme Anticancer Potential of Propolis.” Green Med Info. N.p., 4 Feb. 2014. Web. 16 Feb. 2016.
[xxiii] Sawicka, Diana. “The Anticancer Activity of Propolis.” FOLIA HISTOCHEMICA ET CYTOBIOLOGICA 50.1 (2012): 25-37. Via Medica. Web. 16 Feb. 2016. <https://journals.viamedica.pl/folia_histochemica_cytobiologica/article/viewFile/FHC.2012.0004/14703>.
[xiv] Shailasree, S. “Cytotoxic Effect of P-Coumaric Acid on Neuroblastoma, N2a Cell via Gen.” Molecular Neurobiology 51.1 (2015): 119-30. Springer Link. Web. 16 Feb. 2016. <http://link.springer.com/article/10.1007/s12035-014-8700-2>.
* * *