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Artemisinin Therapy Research

Artemisinin therapy provides cancer patients with additional support during traditional cancer treatments. There are many potential benefits from this therapy, such as effectively destroying cancer cells while avoiding healthy cells.

We offer artemisinin therapy for cancer patients looking to complement their traditional cancer treatments. 

At Wellbeing Medical Group, we’re dedicated to providing you with therapies that are well-researched so you can feel confident in your decision to undergo complementary cancer therapies.

Supporting research for artemisinin therapy

Artemisia annua, which is often known as sweet sagewort or wormwood, has been used in traditional Chinese Medicine for malaria, fevers, inflammation, bleeding and headaches. In vitro studies show that artemisinin, which is the active principle of artemisia annua, may be an effective way of treating African sleeping sickness and protozoal infections and Chagas disease9.

Cytotoxic effects of A. annua compounds have also been evaluated in tumour cell lines1,18-20,25,26. Artemisinin-based combination therapies are part of the standard treatment used for malaria. Reviews have indicated that it is as effective as quinine4 5, but that its uses may be limited because of an increased risk of relapse6,7. It is also unclear whether it is effective against quinine-resistant malaria strains. Additional drug development is being pursued after reports of artemisinin-based therapy resistance also appeared28. 

There are limited studies on artemisia for other health conditions. In one RCT, a low-dose artemisia formulation shows clinically relevant pain reductions in patients with hip or knee osteoarthritis3. A recent study has indicated long-term safety with improvements maintained at 6 months. Studies in advanced cancer patients have suggested that oral add-on artesunate, an artemisinin derivative, is well tolerated, although ototoxicity monitoring is needed13,21. Different studies showed that oral artesunate did not produce a response29,30, although modest clinical activity was seen with intravenous administration30. Further research is needed to determine the conditions under which compounds derived from artemisia may be safe and effective. 

The active component of A. annua, Artemisinin, makes use of its antimalarial effects by free radicals formed via cleavage of the endoperoxide bond in its structure, which are responsible for eradicating the Plasmodium species23. It also induces apoptosis and cell cycle arrest of Leishmania donovani promastigotes8, has antiproliferative effects on medullary thyroid carcinoma cells2, and by modulating p38 and calcium signalling14, induces apoptosis in a lung cancer cell line. 

Research has indicated that it significantly inhibited cell growth and proliferation, and caused G1 cell-cycle arrest in neuroblastoma cell lines25. Dihydroartemisinin, a semi-synthetic derivative of artemisinin, demonstrates anti-inflammatory activity by attenuating COX-2 production via downregulation of serine/threonine kinase and MAPK  pathways24. Recent findings suggest that dihydroartemisinin-triggered apoptosis in colorectal cells occurs through the ROS-mediated mitochondria-dependent pathway26. 

Artemisinin works as a hormone regulator, specifically reducing excess prolactin and oestrogen in breast cancer. It is activated by ionic ferrous iron, which cancer cells accumulate. Iron is an essential compound for cancer cell proliferation. Most cancer cells have high rates of iron intake and express a high concentration of transferrin receptors on the cell surface. The rapid growth of abnormal cells utilise relatively large amounts of iron mainly in the form of holotransferrin. 

Dihydro-artemisinin has a peroxide bond that is activated by iron to generate hydrogen peroxide. This free radical of oxygen stresses cancer cells, which are always deficient in peroxide-neutralising catalase enzymes. Normal cells with catalase can harmlessly dissipate the peroxides. Healthy cells are approximately 100 times less vulnerable to dying from artemisinin than cancer cells. In cancer cells the high-valent oxo iron species create a surge of endoperoxides, depolarizing the mitochondrial membranes and causing a disruption in the electron transport chain.

Other important actions of artemisinin: 

  • Essential in the regulation of P53 DNA repair genes and cyclin-dependent kinases. 
  • Induces apoptosis and slows growth in cancers such as fibrosarcoma, lymphoma,  breast, pancreatic, oesophagal, prostate, and ovarian/fallopian/peritoneal carcinomas,  squamous cell carcinomas and liver hepatocellular cancer.
  • Artemisinin eases the down-regulation of nuclear factor kappa B, which is the master control gene for inflammation. A sign of intense inflammation in the cancer cell is high blood levels of CRP and ESR, and also mid- to high-normal LDH. These markers can help to indicate which patients are good candidates for artemisinin therapy. 
  • Aids in the inhibiting angiogenesis, which disrupts the blood supply to tumours. 
  • Regulates important epigenetics or DNA silencing, including methylation and histone protein acetylation. 
  • Targets translationally controlled tumour protein TCTP – inhibits cysteine protease enzyme, and also a SERCA-type calcium transporter enzyme.

What makes the properties of artemisinin and its derivatives integral components of complementary cancer therapy are its anti-neoplastic properties. While being tested by the  National Cancer Institute in the USA, specifically for its anti-cancer activity on 55 of the most common cancer cell lines, the study23 showed breast, prostate, ovary, colon,  kidney, CNS and melanoma cells showed an increased Artesunate sensitivity. Further research noted a specific sensitivity to diffuse large B-cell lymphoma cells24,25. Clinical studies on patients with breast, cervical, liver and lung cancer have shown tumour reductions of up to 70%, a short-term increase in lifespan and even remission26-28. 

Artemisinin derivatives also showed synergistic effects with chemotherapeutic agents.  When used in combination with gemcitabine in pancreatic carcinoma, growth inhibition was increased fourfold in vitro and in vivo, with the apoptosis rate also being doubled compared to monotherapy with gemcitabine29. An additional study indicated increased inhibition of metastasis and cancer cell growth in murine Lewis lung carcinoma cell lines when used in conjunction with cyclophosphamide compared to monotherapy30. 

Cancer cells are often characterised by developed resistance to chemotherapeutic agents.  A combination of artesunate with doxorubicin and pirarubicin showed increased cytotoxicity in K562/ADR leukaemia and GLC4/ADR lung carcinoma cells31. Along with the above, sensitization was also seen in combination with cisplatin in ovarian carcinoma32. Even independent of p53 status, artemisinin was capable of inducing strong sensitization to gemcitabine in hepatocellular carcinoma cells33. 

Due to artemisinin and its derivatives ability to selectively disrupt tumour growth, its cell cycle and proliferation pathways34, it has an anti-carcinogenic effect. This process can be traced back to the particular properties of the tumour cells, such as increased metabolism, increased blood flow and thus increased iron and transferrin levels. In conjunction with being well tolerated, artemisinin derivatives are also known to have an anti-neoplastic effect.

The anti-carcinogenic effect is based on the structural endoperoxide bridge, which can form cytotoxic radicals with heme groups or intracellular iron. These radicals primarily lead to cell cycle arrest and disrupt proliferative pathways35-37. 

The reason for this specific effect against cancer cells is due to their increased metabolism, their increased requirement for iron and their increased number of transferrin receptors when compared to normal cells38-42. 

In addition, artemisinin and its derivatives were able to induce various cellular signalling pathways that led to apoptosis or necrosis in gastric and oesophageal tumour cell lines44-47. Along with this, artemisinin derivatives showed a reduction in the risk of metastasis by increasing cell adhesion48.

Adverse effects  

Case reports 

  • Hepatitis: In a 52-year-old man following consumption of an herbal supplement containing artemisinin17. 
  • Acute cholestatic hepatitis: In a patient due to ingestion of artemisia tea as prophylaxis against malaria31. 
  • Delayed hemolytic anaemia: Two cases after either oral or intravenous therapy with artemisinin-based treatment for malaria32,33. It is thought this reaction may be related to higher parasite loads32. 
  • Ototoxicity and vertigo: Possibly related to oral artesunate, an active artemisia compound, among several advanced breast cancer patients in a safety trial13,21. The study drug was otherwise largely well tolerated among patients.
  • Dermatitis: With topical use of artemisia11. 

Drug interactions 

CYP450 substrates: In laboratory studies, artemisia extracts induced CYP2B6 and  CYP3A427 and may affect the serum concentration of drugs metabolised by these enzymes. Clinical relevance has yet to be determined. 

Book your artemisinin therapy with Wellbeing Medical Group

If you want to find out more about artemisinin therapy or book your appointment, get in touch with our team today. We’ll guide you through the process and ensure you receive the right complementary therapy for your needs.  

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References

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  2. Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. 1994  Feb;601:54-7. Available from: https://pubmed.ncbi.nlm.nih.gov/8134418/ 
  3. Stebbings S, Beattie E, McNamara D, et al. A pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee. Clin  Rheumatol. Jul 2016;357:1829-1836. Available from: https://pubmed.ncbi.nlm.nih.gov/26631103/  
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  7. Blanke CH, Naisabha GB, Balema MB, et al. Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial. Trop Doct. Apr 2008;382:113-116. Available from: https://pubmed.ncbi.nlm.nih.gov/18453510/  
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  39. Weifeng, T.; Feng, S.; Xiangji, L.; Changging, S.; Zhiquian, Q.; Huazhong, Z.; Peining, Y.; Yong, Y.;  Mengchao, W.; Xiaoqing, J.; et al. Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells. Phytomedicine 2011, 18, 158–162. https://pubmed.ncbi.nlm.nih.gov/20739158/