Somehow I have a very good feeling about this one. I came to this component via research on cardiac glycosides (CG). One of the main active ingredient in Huachansu Zhusheye is Bufalin which is a cardiac glycoside.
Huachansu Zhusheye is a Chinese medicine that can be administrated both orally or IV and is accessible to anyone as it is available at regular pharmacies in China, at low cost. HuaChanSu (bufo bufo gargarizans) is a traditional Chinese medicine extracted from the skin of the Bufo toad. The skin of the Bufo toad secretes a venom which is dried and dissolved in water. Ref.
These category of elements, GCs, which I like a lot, have serious anticancer effects and that is due to their interference with Potassium dynamics. Potassium dynamics is important for cell survival and cancer cells seem to be specifically sensitive to the changes in the Potassium gradient. Indeed, interest in the links between CGs and cancer began to raise in the late 1970s, owing to the discoveries that malignant cells exhibit alterations in the activity of the Na+/K+-ATPase. Other anticancer elements from this category that I intend to address on this website in the future are Oleander, Ouabain (g-strophanthin).
CGs may exert antineoplastic effects not only as they preferentially inhibit the growth of malignant cells, but also as they promote the activation of tumor-specific immune responses. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601180/#!po=10.0000
In the US clinical trial six patients (40%) had prolonged stable disease or minor tumor shrinkage: Pilot Study of Huachansu in Patients With Hepatocellular Carcinoma, Nonsmall-Cell Lung Cancer, or Pancreatic Cancer http://onlinelibrary.wiley.com/doi/10.1002/cncr.24602/pdf
Inhibitors of cellular Na+/K+-ATPase. This ion transport system moves sodium ions out of the cell and brings potassium ions into the cell. This transport function is necessary for cell survival. Loss of these ion gradients would lead to cellular depolarization and loss of the negative membrane potential that is required for normal cell function. The Na+/K+-ATPase also plays an active role in the membrane potential. By inhibiting the Na+/K+-ATPase, cardiac glycosides cause intracellular sodium concentration to increase. This then leads to an accumulation of intracellular calcium via the Na+-Ca++ exchange system.
Cardiac Glycosides exhibit a high bioavailability (> 75%) and readily cross both the blood-brain and the placental barriers.
Inhibitor of Topoisomerase 2 inhibitor
Inhibitor of PI3K-AKT-mTOR pathway (Ref.)
Great overview on mechanism, toxicity, etc: Ref
Safe based on clinical trials performed, in the dose range indicated below.
Toad Venom In Cancer Treatment: Traditional Chinese Medicine Is Well-tolerated, Study Shows http://www.sciencedaily.com/releases/2009/09/090924101638.htm
A cardiac glycoside decreases intracellular magnesium, thereby causing increased urinary magnesium loss. Magnesium deficiencies induced by concomitant diuretic use are very common in individuals using digoxin. Therefore, add magnesium http://www.naturalnews.com/DrugWatch_Digoxin.html
Preparation & Administration
According to the drug instructions: Intramuscular injection, a 2 ~ 4 ml 2x/day; intravenous infusion, 1x/day, 10 ~ 20 ml in 250-500ml NaCl bag slowl drip, administrated each day during 7 days, rest 1 ~ 2 days, and can be started again. http://www.zhongyi001.com/portal.php?mod=view&aid=23948
According to clinical trial in US: Patients were treated in cohorts of 3 per dose level at 5 dose levels. For each subsequent cohort of patients, dose escalation depended on the toxicity profile in the previous cohort. The typical dose of huachansu used in China is 20-25 mL (approximately 15 mL/m2 ). The planned dose escalation schedule for huachansu was as follows; level 1, 10 mL/m2 ; level 2, 20 mL/m2 ; level 3, 40 mL/m2 ; level 4, 60 mL/m2 ; and level 5, 90 mL/m2 . The treatment was repeated daily for 14 days followed by 7 days off (1 cycle). In the absence of treatment delays, treatment was continued beyond 2 cycles. After 2 cycles, most patients received other treatments in combination with huachansu.Plasma bufalin concentration reached maximal levels at the end of the 2-hour infusion and was proportional to the amount of drug being administered (0.81-3.38 ng/mL). Ref
– The doses generally used in China are 20 mL/m2 or 20-25 mL (i.e. approximately 15 mL/m2 )
– The dose in the US trial was from 10 mL/m2 up to 90 mL/m2 with no toxicity Ref
– IV time is about 2 hours
Conversion of mg/kg to mg/ https://ncifrederick.cancer.gov/lasp/acuc/frederick/Media/Documents/ACUC42.pdf
A person of 52kg has 52/37 m2, i.e. 1.4m2
Therefore, for that person, considering 25ml/m2 dose, we need to apply 1.4*25ml=35ml huachansu solution
Note: One person showed response even at 10ml/m2, i,e, 14ml solution for a 52kg person.
Source & Cost
Pharmacies in China, e.g. http://www.zhongyi001.com/portal.php?mod=view&aid=23948
The price in the range of 20$ to 60$/IV depending on the dose used.
Synergists & Antagonists
Clinics Treating Patients with Bufalin
In Germany, any clinic may treat the patient with this drug as long as the patient will come with it.
Other relevant links:
Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening. http://www.ncbi.nlm.nih.gov/pubmed/22999104
Na+/K+-ATPase Î±3 mediates sensitivity of hepatocellular carcinoma cells to bufalin. http://www.ncbi.nlm.nih.gov/pubmed/21181095/
Huachansu injection inhibits metastasis of pancreatic cancer in mice model of human tumor xenograft http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320457/
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