Artemisia Annua
Also known by these names
- Annual wormwood
- Artemisinin (derivative used in cancer)
- Qing Hao
- Qinghaosu
- Sweet Annie
- Sweet sagewort
- Sweet wormwood
- Semi-synthetic drug derivatives:
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Key Points
- The Artemisia annua plant contains chemical compounds effective against malaria that are also considered to have anticancer activity.
- Artemisia annua is of interest to BCCT because of evidence from lab and animal studies suggesting its anticancer properties.
- Case studies and preliminary clinical trials have shown anticancer effects in human patients.
- Safety and dosing in cancer are not established.
- In doses used for malaria, it is generally well tolerated, but with some notable side effects, interactions, cautions and contraindications. These include toxicity to fetuses and liver toxicity. Caution and medical supervision are advised.
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The Artemisia annua plant contains chemical compounds effective against malaria and also considered to have anticancer activity. Artemisinin is a natural derivative of Artemisia annua, and artesunate is a prescription medication derived from Artemisia annua.
Treating the Cancer
Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action
Artemisinin's anticancer activity is believed to occur when it comes in contact with iron. Cancer cells concentrate iron for use in cellular division (the malaria parasite also collects high concentrations of iron). Artemisinin's contact with iron triggers the release of free radicals between cells that destroy cancer cells. Because of this “ferroptosis” effect, iron is often administered several hours before artemisinin to enhance targeting of the cancer cells while sparing normal cells.
Clinical Evidence
Case studies and preliminary clinical trials have shown anticancer effects in human patients:
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- Colorectal cancer
- Lung cancer, advanced non small-cell: standard combination vinorelbine and cisplatin combined with IV artemisinin was effective and well tolerated.
- Melanoma
- Prostate cancer
Lab and Animal Evidence
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A 2017 review article discusses the synergistic and additive anticancer effects of combining artemisinin-type drugs with conventional cancer treatments as well as with some established drugs for indications other than cancer: novel synthetic compounds, natural products and natural product derivatives, therapeutic antibodies and recombinant proteins, and RNA interference. The author also reviews the effects of artemisinin-type drugs towards multidrug-resistant cells and tumor cells with other drug-resistance phenomena. The author concludes that artemisinin and its derivatives exert profound activity against tumor cells both in lab studies and in animals. In clinical oncology, artemisinin-derived therapies seem most promising as part of combination therapy regimens rather than alone.
Artemisinin and its derivatives (especially artesunate) have demonstrated strong anticancer potential in various types of cancer cells, including inhibiting tumor growth and metastasis and prolonging survival:
- Brain cancer
- Breast cancer: one study shows that artesunate activates mitochondrial cell death (apoptosis) in breast cancer cells, while a second study, looking at lab and animal data, found that highly metastatic breast tumors tend to become resistant to artesunate. Artemisinin Inhibited viabiilty and adhesion of breast cancer cells and inhibited tumor growth and metastasis and prolonged survival in various types of breast cancer and other cells
- Endometrial cancer
- Gastric cancer
- Liver cancer
- Oral squamous cell carcinoma
- Pancreatic cancer
- Renal cell carcinoma
- Sarcoma
- Ovarian cancer:
- Anticancer effects including induced autophagy, blocked cell cycle, and inhibited cell growth in ovarian cancer cells
- Anti-proliferative and toxic effects on ovarian cancer cells
- Enhanced toxicity to human ovarian cancer cells without appreciable toxicity to normal cells when conjugated with the chemotherapy drug melphalan in ARS4
- Increased rate of apoptosis when used with doxorubicin in cell studies
- Sensitized ovarian cancer cells to cisplatin and potentiated its effects in cells
- Sensitized human ovarian cancer cells to carboplatin
- A combination of dihydroartemisinin—the active metabolite of all artemisinin compounds—and curcumin showed synergistic antitumor effects in ovarian cancer cells and animals
Cautions
At doses used to treat malaria, Artemisia-derived drugs are generally safe and well tolerated, but no phase I clinical trials have tested the safety of higher doses that are likely required for treating cancer. Doses used in animal studies have been much higher than those used in anti-malaria treatment.
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Some potentially serious side effects and drug interactions with Artemisia annua and/or its derivatives are noted, as well as contraindications and cautions.
- Artemisinin during pregnancy may cause harm to the fetus.
- Artemisinin, when combined with oxidative chemotherapies or radiation, may cause toxicity, especially liver toxicity. Efferth reports two case studies of patients with glioblastoma who received artemisinin-type drugs that resulted in liver toxicity in both cases and bone marrow suppression and death in the second case. The treatment drugs were combined with chemotherapy and Chinese herbs in the first case and dichloroacetic acid in the second case. Monitoring liver function routinely is advised.
- A number of articles report interactions between Artemisia annua or its derivatives with drugs and/or natural products.
- Long-term use (up to 37 months) in metastatic breast cancer patients did not result in any major safety concerns.
Consult with your pharmacist for interactions, and discuss using Artemisia annua or its derivatives with your doctor. BCCT suggests that patients who use Artemisia for cancer seek guidance for usage, dose and formulation from an integrative cancer care clinician or traditional Chinese medicine practitioner with experience working with cancer patients.
Access
Plant leaves and powdered and liquid extracts are available for purchase in the US. Artemisinin, a natural derivative of Artemisia annua, is available for purchase as a supplement.
Artesunate, the synthetic drug derived from the Artemisia plant, is available by prescription in the US only for patients who have a documented case of severe malaria. It is used widely in European cancer clinics providing complementary therapies.
Dosing
Exact dosage of the herb Artemisia annua in cancer has not been determined in clinical trials. Concentrations of the active ingredients vary among products. See Quality and Sources of Herbs, Supplements and Other Natural Products for general information.
Integrative cancer care plans, protocols and references listed below suggest doses. For a lengthy discussion of dosages of the various plant and supplement derivatives of Artemisia annua, artemisinin and artesunate, see these sources:
Integrative Programs, Protocols and Medical Systems
A number of European complementary and alternative medicine cancer clinics use this natural product, and Chinese researchers consider it a very promising anticancer therapy.
- Programs and protocols
- Alschuler & Gazella complementary approaches:
- Head and neck cancer
- Prostate cancer
- Bastyr University Integrative Oncology Research Center protocol for Stage IV Breast Cancer
- Chang strategies
- McKinney protocols
- General cancer
- Breast cancer
- Carcinoid/neuroendocrine cancer
- Cervical cancer
- Colorectal cancer
- Esophageal cancer
- Fibrosarcoma
- Gallbladder cancer
- Head and neck cancer
- Kidney cancer
- Leukemia
- Liver cancer
- Lung cancer
- Lymphoma
- Multiple myeloma
- Myelodysplastic syndrome
- Ovarian cancer
- Pancreatic cancer
- Prostate cancer
- Stomach cancers
- Traditional systems
Lise Alschuler, ND, FABNO, advises avoiding using artemisinin during radiation therapy and for an additional 30 days after therapy ends.
Keith Block, MD, advises: “Until we have more research, I advise not taking this herbal while you are undergoing conventional treatment.”
Non-cancer Uses of Artemisinin
BCCT has not reviewed the effectiveness of this therapy for non-cancer uses.
- Fever
- Headaches
- Infections
- Inflammation
- Malaria and other protozoal infections including leishmaniasis, Chagas disease and African sleeping sickness
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Written by Laura Pole, RN, MSN, OCNS, and reviewed by Nancy Hepp, MS; last update April 18, 2019. Note: BCCT has not conducted an independent research of Artemisia annua. This summary draws from these sources and other as cited:
- Krishna S, Ganapathi S et al. A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine. 2014 Nov 15;2(1):82-90.
- Zhang ZY1, Yu SQ et al. [Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial]. [Article in Chinese]. Zhong Xi Yi Jie He Xue Bao. 2008 Feb;6(2):134-8.
- Berger TG, Dieckmann D et al. Artesunate in the treatment of metastatic uveal melanoma--first experiences. Oncology Reports. 2005 Dec;14(6):1599-603.
- Michaelsen FW, Saeed ME, Schwarzkopf J, Efferth T. Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma. Phytomedicine. 2015 Dec 15;22(14):1223-31.
- Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
- Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. Journal of Biomedicine and Biotechnology. 2012;2012:247597; Zyad A, Tilaoui M, Jaafari A, Oukerrou MA, Mouse HA. More insights into the pharmacological effects of artemisinin. Phytotherapy Research. 2017 Nov 28.
- Kast RE, Karpel-Massler G, Halatsch ME. CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget. 2014 Sep 30;5(18):8052-82.
- Hamacher-Brady A, Stein HA et al. Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. Journal of Biological Chemistry. 2011 Feb 25;286(8):6587-601.
- Bachmeier B, Fichtner I et al. Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells. PLOS ONE. 2011;6(5):e20550.
- Ko YS, Lee WS et al. Polyphenols from Artemisia annua L inhibit adhesion and EMT of highly metastatic breast cancer cells MDA-MB-231. Phytotherapy Research. 2016 Jul;30(7):1180-8.
- Worku N, Mossie A et al. Evaluation of the in vitro efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk extracts in cancer and Trypanosoma brucei cells. ISRN Biochemistry. 2013 Sep 22;2013:910308.
- Tran KQ, Tin AS, Firestone GL. Artemisinin triggers a G1 cell cycle arrest of human Ishikawa endometrial cancer cells and inhibits cyclin-dependent kinase-4 promoter activity and expression by disrupting nuclear factor-κB transcriptional signaling. Anticancer Drugs. 2014 Mar;25(3):270-81.
- Zhou X, Sun WJ et al. Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo. Anticancer Drugs. 2013 Oct;24(9):920-7.
- Wang Q, Wu LM, Li AY, Zhao Y, Wang NP. [Experimental studies of antitumor effect of artesunate on liver cancer]. [Article in Chinese]. Zhongguo Zhong Yao Za Zhi. 2001 Oct;26(10):707-8, 720; Vandewynckel YP, Laukens D et al. Therapeutic effects of artesunate in hepatocellular carcinoma: repurposing an ancient antimalarial agent. European Journal of Gastroenterology and Hepatology. 2014 Aug;26(8):861-70.
- Yamachika E, Habte T, Oda D. Artemisinin: an alternative treatment for oral squamous cell carcinoma. Anticancer Research. 2004 Jul-Aug;24(4):2153-60.
- Du JH, Zhang HD, Ma ZJ, Ji KM. Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemotherapy and Pharmacology. 2010 Apr;65(5):895-902.
- Jeong DE, Song HJ et al. Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis. Oncotarget. 2015 Oct 20;6(32):33046-64.
- Breuer E, Efferth T. Treatment of iron-loaded veterinary sarcoma by Artemisia annua. Natural Products and Bioprospecting. 2014 Apr;4(2):113-8.
- Li B, Bu S, Sun J, Guo Y, Lai D. Artemisinin derivatives inhibit epithelial ovarian cancer cells via autophagy-mediated cell cycle arrest. Acta Biochimica et Biophysica Sinica (Shanghai). 2018 Dec 1;50(12):1227-1235; Liu Y1,2, Gao S et al. Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway. Cancer Medicine. 2018 Nov;7(11):5704-5715; Li X, Ba Q et al. Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein. Cell Discovery. 2017 Nov 21;3:17042.
- Greenshields AL, Shepherd TG, Hoskin DW. Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Molecular Carcinogenesis. 2017 Jan;56(1):75-93.
- Li X, Zhou Y et al. Preclinical efficacy and safety assessment of artemisinin-chemotherapeutic agent conjugates for ovarian cancer. EBioMedicine. 2016 Dec;14:44-54.
- Tai X, Cai XB, Zhang Z, Wei R. In vitro and in vivo inhibition of tumor cell viability by combined dihydroartemisinin and doxorubicin treatment, and the underlying mechanism. Oncology Letters. 2016 Nov;12(5):3701-3706.
- Wang B, Hou D et al. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer, Biology & Therapy. 2015;16(10):1548-56; Feng X, Li L et al. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy. Biochemical and Biophysical Research Communications. 2014 Feb 14;444(3):376-81.
- Chen T, Li M, Zhang R, Wang H. Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy. Journal of Cellular and Molecular Medicine. 2009 Jul;13(7):1358-70.
- Zhao J, Pan Y et al. Dihydroartemisinin and curcumin synergistically induce apoptosis in SKOV3 cells via upregulation of MiR-124 targeting midkine. Cell Physiology and Biochemistry. 2017;43(2):589-601.
- Alschuler LN, Gazella KA. The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, California: Celestial Arts. 2010. p. 162.
- Block KI. Life Over Cancer. New York: Bantam Dell. 2009. p. 476; Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
- Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
- Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
- von Hagens C, Walter-Sack I et al. Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).Phytomedicine. 2018 Sep 17;54:140-148.
- Alschuler LN, Gazella KA. The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, California: Celestial Arts. 2010; p. 388.
- Alschuler LN, Gazella KA. The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, California: Celestial Arts. 2010.
- McKinney N. Naturopathic Oncology, 3rd Edition. Victoria, BC, Canada: Liaison Press. 2016, p. 316 .
- Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
- McKinney N. Naturopathic Oncology, 3rd Edition. Victoria, BC, Canada: Liaison Press. 2016.
- Alschuler LN, Gazella KA. The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, California: Celestial Arts. 2010.
- Block KI. Life Over Cancer. New York: Bantam Dell. 2009. p. 476.
View All References
More Information
- Memorial Sloan Kettering Cancer Center’s About Herbs: Artemisia annua
- CAM-Cancer: Artemisia
- Mihaela Catalina Stanciu Foundation for Life: Artemisia annua, Artemisinin & 2015 Nobel Prize in Medicine
- Chang R. Beyond the Magic Bullet: The Anti-Cancer Cocktail. New York: Square One Publishers. 2012.
- TRC Natural Medicines: Artemisinin Herba-Alba and Sweet Annie (subscription required): in-depth information, ratings of effectiveness and safety and evaluation of specific Artemisia products
- Consumer Labs: Product Review (subscription is required): Wormwood
- Keith I. Block, MD: Life over Cancer: The Block Center Program for Integrative Cancer Treatment
- Lise Alschuler, ND, FABNO, and Karolyn Gazella: The Definitive Guide to Cancer, 3rd Edition
- American Botanical Council: HerbMed
- Lone Star Medical Group: Natural Alternative Treatments
- Neil McKinney, BSc, ND: Naturopathic Oncology, 3rd Edition
- Donald I. Abrams, MD, and Andrew T. Weil, MD: Integrative Oncology, 2nd Edition
- Dwight McKee, MD, editor: Clinical Pearls
- Barbara MacDonald, ND, LAc: The Breast Cancer Companion: A Complementary Care Manual: Third Edition
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