Once again, the indefatigable Narendra Singh (half of the UDub team of Lai and Singh that has led much of the in vitro and in vivo research on artemisinin and cancer) have published a case history in the Journal of Integrative Cancer Therapeutics. Interestingly in this case, the patients typical macroadenoma symptoms resolved with the ART treatment, although the lesion was still visible on CT. For CNS lesions we too have recommended artemether (a more lipophilic artemsinin derivative) which theoretically has superior blood brain barrier traversing properties. Full text available temporarily at Sage Publications site…
Singh, N. P. and V. K. Panwar (2006). “Case report of a pituitary macroadenoma treated with artemether.” Integr Cancer Ther 5(4): 391-4.
Introduction: This report describes the case of a male patient with pituitary macroadenoma treated with the artemisinin analog artemether. Patient and METHODS: A 75 year-old male patient presented with vision, hearing, and locomotion-related problems. Artemether was administered orally to the patient over a period of 12 months. RESULTS: Although the tumor remained consistent in size, CT scan shows a reduction in its density, and clinically, the related symptoms and signs resolved significantly as therapy progressed. Discussion: Overall, the artemether treatment was beneficial in improving the patient’s quality of life. Artemether and other artemisinin analogs offer promise for cancer therapy.
Sage ICT linkout (pdf full text)
Remember the recent paper by well known artemisinin researchers Lai and Singh from U-Dub in Washington state (HERBLOG flashback)? Well Holley Pharmaceuticals have made available a sodium butyrate preparation - in capsules. Of course they do not say what the recommended dose of butyrate is - the bad news is that to attain 1.0 millmolar plasma levels that approximate the experimental concentrations that produced a ten fold increase in artemisinin effect - you need to take at least 10 grams (10,000 mg ) a day.In brain tumors, doses up to 20 g /day have been used. The Holley caps contain 600 mg sodium butyrate, so thats about 16-30Â caps per day. A lot.
The good news is that butyrate is totally non toxic (its a food ingredient found typically in butter) and is a selective nutrient for colonocytes. At these high doses the main side effect is…body odor. Oh well. 10 x synergy with artemsinin is worth a bit of a stink.
Butyrate acts as a class of anticancer agent called ‘histone deacetylase inhibitors” - and has been used alone and in combination with other drugs as an anticancer therapy. It is not clear whether affecting histones is the mechanism of sensitization to artemisinin - probably not, but at this stage we do not know.
The literature on artemisinin and its derivatives in relation to malaria and cancer is increasing rapidly. This bibliography is a selected list of key articles for practitioners and others who may be considering artemisinin use. It primarily relates to cancer, with malaria pharmacodynamics included insofar as they are relevant to antineoplastic effects. Also includes pharmacokinetics and toxicology, with some additional references on soluble transferrin receptors (STr is an essential lab index for assessing iron status prior to artemisinin treatment). To be updated periodically.
Artemisa annua - Select bibliography (pdf)
Singh, N. P. and H. C. Lai (2005). “Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.”Anticancer Res 25(6B): 4325-31.
BACKGROUND: Butyric acid is a short chain fatty acid produced by large bowel bacterial flora. It serves as an antiinflammatory agent and nutrient for normal colon cells. Butyric acid has also been shown to induce apoptosis in colon and many other cancer cells. Artemisinin is a compound extracted from the wormwood Artemisia annua L. It has been shown to selectively kill cancer cells in vitro and to be effective in treating animal and human cancer. We and others have found that the artemisinin analog, dihydroartemisinin (DHA), kills cancer cells by apoptosis. In the present study, the efficacy of a combined treatment of DHA and butyric acid at low doses in killing cancer cells was investigated. MATERIALS AND METHODS: Molt-4 cells (a human lymphoblastoid leukemia cell line) and freshly isolated human lymphocytes, cultured in complete RPMI-1640 medium, were first incubated with 12 microM of human holotransferrin at 37 degrees C in a humid atmosphere of 5% CO2 for one hour to enhance the iron concentration in the cells. Cells from each cell type were then divided into 20 flasks. These flasks were grouped into four sets of five cultures each. Zero, 5, 10 or 20 microM of DHA was added, respectively, to these sets and the cells were incubated at 37 degrees C for one hour. Zero, 1, 5, 10, or 20 mM of sodium butyrate was then added to the five cultures of each set, respectively. Thus, the treatments involved a combination of 4 doses of DHA and 5 doses of sodium butyrate. The cells were counted immediately before the addition of DHA, and at 24 and 48 hours after the addition of sodium butyrate. RESULTS: DHA alone at the 24-hour time-point and 20 microM concentration significantly reduced the number of Molt-4 cells in the culture by approximately 40% (p < 0.001, compared to non-treated control), whereas it did not significantly affect the number of normal human lymphocytes. Similarly, 1 mM sodium butyrate alone at 24 hours reduced the number of Molt-4 cells by approximately 32% (p < 0.001, compared to non-treated control), without significantly affecting normal human lymphocytes. The combination of 20 microM DHA and 1 mM sodium butyrate killed all Molt-4 cells at the 24-hour time-point and did not significantly affect lymphocytes. CONCLUSION: DHA in combination with butyric acid acts synergistically at low doses. The combination may provide a less toxic, inexpensive and effective cancer chemotherapy.
JT Comment
This is interesting! Butyrate is non toxic, and is active on its own against several cancers. Doses are likely to be high however, about 600 mg/Kg po which may be an issue. Watch this space.