L'artemisinine, une nouvelle voie pour traiter certains cancers ?

Dr Bernard Auriol

(extraits de Environmental News Network Inc., 2001)

Annual wormwood (Artemisia annua and not Absinthe) is the Basis for a Cancer-fighting Pill
31 January 2002

A nontoxic pill that could be taken on an outpatient basis to combat breast cancer or leukemia sounds like a fantasy, but the treatment is becoming a reality due to the investigation of a University of Washington research team into an ancient Chinese remedy for malaria.

Research professor Henry Lai and assistant research professor Narendra Singh have exploited the chemical properties of a [annual] wormwood derivative to target breast cancer cells with surprisingly effective results. A study in the latest issue of the journal Life Sciences describes how the derivative killed virtually all human breast cancer cells exposed to it within 16 hours.

"Not only does it appear to be effective, but it's very selective," Lai said. "It's highly toxic to the cancer cells but has a marginal impact on normal breast cells."

[…]

The use of the bitter herb [annual] wormwood is nothing new. Used for centuries to rid the body of worms […].

Artemisinin, the compound that Lai and Singh have found to fight cancers, isn't new either. It was extracted from the plant Artemesia annua L., […], thousands of years ago by the Chinese, who used it to combat the mosquito-borne disease malaria. The treatment with artemisinin was lost over time but rediscovered during an archaeological dig in the 1970s that unearthed recipes for ancient medical remedies.

Now widely used in Asia and Africa to fight malaria, artemisinin reacts with the high iron concentrations found in the malaria parasite. When artemisinin comes into contact with iron, a chemical reaction ensues, spawning charged atoms that chemists call free radicals. The free radicals attack cell membranes, breaking them apart and killing the single-cell parasite.

About seven years ago, Lai began to hypothesize that the process might work with cancer, too.

"Cancer cells need a lot of iron to replicate DNA when they divide," Lai explained. "As a result, cancer cells have much higher iron concentrations than normal cells. When we began to understand how artemisinin worked, I started wondering if we could use that knowledge to target cancer cells."

Lai devised a potential method and began to look for funding, obtaining a grant from the Breast Cancer Fund in San Francisco.

The thrust of the idea, according to Lai and Singh, was to pump up the cancer cells with maximum iron concentrations, then introduce artemisinin to selectively kill the cancer. In the current study, after eight hours, just 25 percent of the cancer cells remained. By the time 16 hours had passed, nearly all the cells were dead.

An earlier study involving leukemia cells yielded even more impressive results. The cancer cells were eliminated within eight hours. A possible explanation might be the level of iron in the leukemia cells. "They have one of the highest iron concentrations among cancer cells," Lai explained. "Leukemia cells can have more than 1,000 times the concentration of iron that normal cells have."

The next step, according to Lai, is animal testing.

Limited tests have been done in that area. In an earlier study, a dog with bone cancer so severe it couldn't walk made a complete recovery in five days after receiving the treatment. But more rigorous testing is needed.

If the process lives up to its early promise, it could revolutionize the way some cancers are approached, Lai said. The goal would be a treatment that could be taken orally on an outpatient basis.

"That would be very easy, and this could make that possible," Lai said. "The cost is another plus: At $2 a dose, it's very cheap. And with the millions of people who have already taken artemisinin for malaria, we have a track record showing that it's safe."

Whatever happens, Lai said, a portion of the credit will have to go to unknown medical practitioners, long gone now. "The fascinating thing is that this was something the Chinese used thousands of years ago," he said. "We simply found a different application."

Artemisia annua is not generally referred to as wormwood but rather Sweet Annie. The Chinese name is Qing hao.

Armoise annuelle (Artemisia annua et pas d'Absinthe) sert de base à une pilule contre le Cancer
31 Janvier 2002

Une pilule non toxique qui pourrait être prise sur une base ambulatoire pour lutter contre le cancer du sein ou la leucémie sonne comme un fantasme, mais le traitement devient une réalité en raison de l'enquête d'une équipe de chercheurs de l'Université de Washington sur un ancien remède chinois contre le paludisme.

Le professeur Henry Lai et le professeur Narendra Singh ont exploité les propriétés chimiques d'un dérivé de l'armoise amère (artemisia annua) pour cibler les cellules cancéreuses du sein avec des résultats étonnamment efficaces. Une étude dans le dernier numéro de la revue Life Sciences (Sciences de la vie) décrit comment ce dérivé tendait à détruire presque toutes les cellules cancéreuses du sein humain, mises à son contact, en moins de 16 heures.

« Non seulement ce produit semble être efficace, mais il serait aussi très sélectif, » d'après Lai. « Il est hautement toxique pour les cellules cancéreuses, mais n'a qu'un impact marginal sur les cellules normales du sein. »

[…]

L'utilisation de l'armoise amère n'est pas nouveau. Elle est utilisée depuis des siècles comme vermifuge [...].

L'artémisinine, ce composé que Lai et Singh ont trouvé pour lutter contre les cancers, n'est pas nouveau non plus. Elle a été extraite de la plante Artemisia annua, [...], depuis des milliers d'années par les chinois, qui l'utilisaient pour lutter contre le paludisme, maladie transmise par les moustiques. Le traitement par artémisine a été perdu au fil du temps, mais redécouvert lors de fouilles archéologiques dans les années 1970 qui ont mis au jour des recettes de remèdes médicaux anciens.

Maintenant utilisée couramment en Asie et en Afrique pour lutter contre le paludisme, l'artémisinine réagit avec les grandes concentrations de fer trouvées dans le parasite du paludisme. Quand l'artémisinine vient en contact avec le fer, il s'ensuit une réaction chimique, les atomes chargées engendrant ce que les chimistes appellent des radicaux libres. Les radicaux libres attaquent les membranes cellulaires, les cassant et tuant le parasite de la cellule.

Il y a environ sept ans Lai a commencé à émettre l'hypothèse que le processus pourrait fonctionner également avec un cancer.

« Les cellules cancéreuses ont besoin de beaucoup de fer pour répliquer l'ADN lorsqu'elles se divisent» a expliqué Lai. "Ainsi, les cellules cancéreuses ont des concentrations de fer beaucoup plus élevées que les cellules normales. Lorsque nous avons commencé à comprendre comment l'artémisinine fonctionne, j'ai commencé a me demander si nous pouvions utiliser ces connaissances pour cibler les cellules cancéreuses. »

Lai a conçu une méthode potentielle et a commencé à chercher des fonds, et il a obtenu une subvention du Breast Cancer Fund à San Francisco.

L'idée maîtresse, selon Lai et Singh, a été de saturer les cellules cancéreuses avec des concentrations maximales de fer, puis d'ntroduire l'artémisinine pour sélectivement tuer le cancer. Dans cette étude, après huit heures, il ne restait plus que 25 % des cellules. Et au bout de 16 heures, presque toutes les cellules étaient mortes.

Une étude antérieure sur les cellules leucémiques avaient donné des résultats encore plus impressionnants. Les cellules cancéreuses avaient été éliminées en moins de huit heures. Une explication possible pourrait être le niveau de fer dans les cellules leucémiques. « Ces cellules ont une des concentrations de fer les plus élevées parmi les cellules cancéreuses », a expliqué Lai. « Les cellules leucémiques peuvent avoir plus de 1 000 fois la concentration de fer de scellules normales. »

La prochaine étape, selon Lai, serait d'effectuer des tests sur les animaux.

Des essais limités ont été réalisés dans ce domaine. Dans une étude antérieure, un chien atteint de cancer des os si grave qu'il ne pouvait pas marcher a été très amélioré en cinq jours après avoir reçu le traitement. Mais des tests plus rigoureux sont nécessaire.

Si le processus est fidèle à ses promesses, selon Lai, il pourrait révolutionner la façon dont certains cancers sont traités. Le but est un traitement qui pourrait être pris par voie orale en ambulatoire.

Selon Lai, « Ce serait très facile, et cela pourrait être possible ». "Le coût est un autre atout: À 2 dollars la dose, ve médicament est très bon marché. Et puisque des millions de personnes ont déjà pris de l'artémisinine contre le paludisme, nous savons qu'il ne s'agit pas d'un produit dangereux. »

Quoi qu'il en soit, déclare Lai, notre reconnaissance doit aller à ces médecins inconnus, disparus depuis longtemps maintenant. « Ce qui est fascinant, c'est qu'il s'agit de quelque chose que les chinois ont utilisé depuis des milliers d'années». « Nous avons simplement découvert une application nouvelle ».

L'Artemisia annua n'est généralement pas dénommée absinthe amère mais plutôt Armoise. Le nom chinois est Qing hao.

Prices for Malarlife: All prices exclude banking and posting costs.

One course of 250mg Malarlife caps '56 = $11.00 USD
Discount prices are available for larger orders.

Contact: malarlife@dfl.org.za

Artemisia annua: The price for Artemisia Annua per 50g is = $15.50 USD
and per 250g = $69.2 USD

Artemesinin lang=EN-US> and its use in fighting various forms of cancer : Please read conditions expressed on the Disclaimer page before continuing, thanks.

"Ancient Chinese Folk Remedy May Hold Key to Non-Toxic Cancer Treatment." Editorial. University of Washington 30 Nov 2001. http://www.sciencedaily.com/releases/2001/11/011127003905.htm

"Ancient Chinese Folk Remedy May Hold Key to Non-Toxic Cancer Treatment." Press Release. University of Washington 26 Nov 2001. http://www.arrowheadhealthworks.com/artemis.htm

"Artemesia: Compound Characteristics." Beerse, Belgium: Dafra Pharma. http://www.dafra.be/english/artemisinin.html

"Artemesia Herb for Cancer." 2nd Opinion May 2002. http://www.laleva.cc/choice/artemisia4cancer.html

"Artemether: Compound Characteristics." Beerse, Belgium: Dafra Pharma. http://www.dafra.be/english/artesunate.html

"Artemisinin." Product Description. Palos Verdes, California: Wellcare Pharmaceutical Co, 1996-2002. http://www.hepalin.com/hepalin100.htm

"Artemisinin: Multifaceted Nutritional Support" Product description. Hayward, California: Nutricology, Mar. 2003. http://www.nutricology.com/proddesc/discuss/NC_ArtemisininPDFProductSheet032403.pdf

"Artemix." Product Description. Palos Verdes, California: Wellcare Pharmaceutical Co, 1996-2002. http://www.hepalin.com/artemix.htm

"Artesunate: Compound Characteristics." Beerse, Belgium: Dafra Pharma. http://www.dafra.be/english/artesunate.html

Beekman AC, Barentsen AR, Woerdenbag HJ, et al: Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J Nat Prod 60:325-330, 1997.

Beekman AC, Wierenga PK, Woerdenbag HJ, et al: Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells. Planta Med 64:615-619, 1998.

Beekman AC, Woerdenbag HJ, Van Uden W, et al: Stability of artemisinin in aqueous environments: impact on its cytotoxic action to Ehrlich ascites tumour cells. J Pharm Pharmacol 49:1254-1258, 1997.

Bhisutthibhan J, Philbert MA, Fujioka H, Aikawa M, Meshnick SR: The Plasmodium falciparum translationally controlled tumor protein: subcellular localization and calcium binding. Eur J Cell Biol 78:665-670, 1999.

"Chinese Herb Triumphs Over Cancer." Alternative Medicine Angel (AltMedAngel) http://members.tripod.com/~altmedangel/cancherb.htm.

"Chinese remedy 'may fight cancer'." BBC News 28 Nov 2001. http://news.bbc.co.uk/1/hi/health/1678469.stm

Dharmananda, Subhuti. "Ching-Hao and the Artemisia Used in Chinese Medicine." Institute for Traditional Medicine Online. Mar. 2002. http://www.itmonline.org/arts/chinghao.htm

Dhingra V, Rao KV, Narasu NL: Current status of artemisinin and its derivatives as antimalarial drugs. Life Sci 66:279-300, 2000.

Efferth T, Dunstan H, Sauerbrey A, et al: The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767-773, 2001.

Efferth T, Davey M, Olbrich A, et al.: Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MDR1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells, Molecules, and Diseases 28:160-168, 2002.

Efferth T, Olbrich A, Bauer R: RNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, artesunate, and artemether. Biochem Pharmacol 64:617-623, 2002.

Evans, Nancy. "Malaria Drug May Hold Key to Nontoxic Treatment: The Breast Cancer Fund (TBCF) Funding Helps Explore Breakthrough Therapy". http://www.breastcancerfund.org/pdfs/news_fall_2001/page6.pdf

Ferreira, Jorge F.S. and Jules Janick. "Distribution of Artemisinin in Artemisia Annua."Progress in New Crops. Arlington, Virginia: ASHS Press, 1996. 579-584. http://www.hort.purdue.edu/newcrop/proceedings1996/v3-578.html#BOTANY

Fishwick J, Edwards G, Ward SA, et al: Binding of dihydroartemisinin to differentiating neuroblastoma cells and rat cortical homogenate. Neurotoxicology 19:405-412, 1998.

Fishwick J, Edwards G, Ward SA, et al: Morphological and immunocytochemical effects of dihydroartemisinin on differentiating NB2a neuroblastoma cells. Neurotoxicology 19:393-403, 1998.

Gilbert, Deborah. "Ancient Chinese fever remedy effective against malaria."The University Record 19 Jul. 1993. http://www.umich.edu/~urecord/9293/Jul19_93/19.htm

"How Ancient Wormwood Extracts Used to Treat Worms & Malaria Were Rediscovered As A Promising Alternative for Breast Cancer Treatment."Product Description. http://www.altcancer.com/artemis.htm

Hu YQ, Tan RX, Chu MY, et al: Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res 91:113-117, 2000.

Insight.com health/chinese-medicine "Iron Homeostasis: Insights From Genetics and Animal Models" Slide. Nature Reviews Genetics 1 (2000) 208-217. http://www.nature.com/nrg/journal/v1/n3/slideshow/nrg1200_208a_F2.html

Lai, Henry and Narendra P. Singh. "Selective Cancer Cell Cytotoxicity From Exposure to Dihydroartemisinin and Holotransferrin." Cancer Letters 91.1. 4 May 1995. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T54-4037SC4-2V&_coverDate=05%2F04%2F1995&_alid=87247126&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4992&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b8b7513c374926e9794fc48b0a9064a9

Lee CH, Hong H, Shin J, et al.: NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin. Biochem Biophys Res Comm 274:359-369, 2000.

Li Y, Shan F, Wu JM, et al: Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 11:5-8, 2001.

McLean WG, Ward SA: In vitro neurotoxicity of artemisinin derivatives. Med Trop (Mars) 58:28-31, 1998.

Moore JC, Lai H, Li JR, et al: Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett 98:83-87, 1995.

Mukanganyama S, Widersten M, Naik YS, et al: Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer 97:700-705, 2002.

Navaratnam V, Mansor SM, Sit NW, et al: Pharmacokinetics of artemisinin-type compounds. Clin Pharmacokinet 39:255-270, 2000.

Olliaro, Piero L., et al. "Pharmacokinetics of artesunate after single oral administration to rats." BioMed Central (BMC) Pharmacology 1:12, 2001. http://www.biomedcentral.com/1471-2210/1/12

Posner GH, Ploypradith P, Parker MH, et al: Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. J Med Chem 42:4275-4280, 1999.

Reungpatthanapong P, Mankhetkorn S: Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC/adr resistant cell lines. Biol Pharm Bull 25:1555-1561, 2002.

Sadava D, Phillips T, Lin C, et al: Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Lett 179:151-156, 2002.

Shaikenov TE, Adekenov SM, Williams RM, et al: Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase. Oncol Rep 8:173-179, 2001.

Singh, Narendra P. "Artemisinin in Cancer Treatment."Seattle, Washington: Dept. of Bioengineering University of Washington. http://www.ctrf.org/cim/pdfs/singh.pdf

Singh NP, Verma KB: Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10:279-280, 2002.

Singh, Narendra P. and Henry Lai. "Selective Toxicity of Dihydroartemisinin and Holotransferrin Toward Human Breast Cancer Cells." Life Sciences 70(1) (21 Nov. 2001): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=f1000&cmd=Retrieve&db=PubMed&list_uids=11764006&dopt=Abstract

Smith SL, Maggs JL, Edwards G, et al. "The role of iron in neurotoxicity: a study of novel antimalarial drugs". Neurotoxicology 19:557-559, 1998.

Sun WC, Han JX, Yang WY, et al. "Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro". Zhongguo Yao Li Xue Bao 13:541-543, 1992.

Thomas, Daniel Josiah. Home Page"Artesunate Treatment."http://www.danieljosiah.com/treatment.htm

University of Washington. Department of Bioengineering. Artemisinin White, Christina L. "Cancer Smart Bomb: Part II Artemisinin Follow-Up." New Horizons Fall 2002. http://www.mwt.net/~drbrewer/canart2.htm

Woerdenbag HJ, Merfort I, Passreiter CM, et al: Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC4 and the COLO 320 cell lines. Planta Med 60:434-437, 1994.

Woerdenbag HJ, Moskal TA, Pras N, et al: Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56:849-856, 1993.

"World Health Organization (WHO) Consultation on clinical neurological investigations required for patients treated with artemisinin compounds and derivatives: Report of an Informal Consultation convened by WHO" 20 Jul. 1998. http://www.who.int/tdr/publications/publications/pdf/artemisinin.pdf

"Wormwood." Digital Naturopath. The Analyst. 28 Jan. 2003. http://www.digitalnaturopath.com/treat/T225441.html

"Wormwood: Artemisia Annua" Product description. Guuelph, Ontario Canada: Nutraceutical Alliance, Inc., 2000. http://www.nutraceuticalalliance.com/hl25.htm

"Wormwood is the Basis for a Cancer-fighting Pill" Environmental News Network, Inc. 28 Nov. 2001. http://www.enn.com/news/enn-stories/2001/11/11282001/s_45678.asp

"Wormwood is the Basis for a Cancer-fighting Pill: Annual Wormwood: Artemisia Annua L." Environmental News Network, Inc. 09 Apr. 2002. http://www.malarlife.dfl.org.za/single%20pages/world_news/31_01_2002.htm

Wu JM, Shan F, Wu GS, et al: Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group. Eur J Med Chem 36:469-479, 2001.

Zheng GQ: Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 60:54-57, 1994.