Hepatocellular carcinoma treatment and experiments with artemisinin

Artemisinin is the first type of drug to treat the basic version of the parasite Plasmodium falciparum or disease better known as malaria. This preparation was isolated from the plant Artemis Annua or popularly called sweet wormwood, which has been one of the leading plants in traditional Chinese medicine for centuries.

Artemisinin has a peroxide bond that gives it the ability to form free radicals after contact with iron. Free radicals are toxic cells. Cancer cells are extremely dependent on iron due to DNA duplication during cell division. For this reason, cancerous cells contain a high concentration of intercellular iron, more than normal cells to be able to supply uncontrolled replication. For that reason, Artemisinin is toxic exclusively to cancer cells.

This invention related to artemisinin has inspired many researchers who have dedicated their work to the study of cancerous diseases and the discovery of new therapy to treat cancer . In addition, artemisinin is less potent than other anti-cancer drugs, so larger amounts of this preparation are needed to achieve the desired effect. For this reason, more effective artemisinin derivatives have been developed and used in clinical trials. These compounds have given promising results as extremely potent drugs with fewer side effects compared to the traditional anti-cancer agents used so far.

Treatment of hepatocellular carcinoma

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Many artemisinin derivatives, both simple and complex, have been tested as a treatment for some types of cancer that occur in humans. The hepatocellular type of cancer is one of them.

Hepatocellular carcinoma has a long developmental time without symptoms and complications present. For this reason, most patients have a highly developed disease with many enlargements and tumors of a high degree at the time it is diagnosed. These results are associated with a very low survival rate that is on average within 5 years of onset.

Hepatocellular cancer treatment options include surgery and chemotherapy. Surgical interventions are not possible in cases with a developed type of tumor. For this reason, pharmacological therapy is extremely important for the treatment of hepatocellular carcinoma.

Traditional chemotherapeutic drugs are not as effective on advanced types of cancer, even when used in combination. This fact adds even more pressure on medicine and scientists to find an alternative to classical methods of treatment.

Gemcitabine

Gemcitabine, the latest broad-spectrum drug with anti-cancer properties, has been included in the latest medical trials for the treatment of hepatocellular carcinoma. Research has yielded positive results so far. Further research was continued with this drug and its combination with artemisinin and its derivatives.

Artemisinin study 1

sweet wormwood artemisia annua

The anti-cancer effects of artemsinin include its effect on apoptosis or the death of cancer cells. The method of action in this direction has not been defined yet.

One study on hepatocellular carcinoma was conducted in China and the leader of the research team was Dr. Junmei Hou. In this study, artemisinin or ART for short and its derivative dihydroartemisinin or DHA, ARM artemether and ARS artesunate were tested in vitro on hepatoma cells HepG2 (p53 wild type), Huh-7 (p53 mutated), BE-7404 (p53 mutated), Hep3B (p53 null) and 7702 (normal liver cells). The effect and variations of artemisinin derivatives on all cell types, both carcinogenic and healthy, were compared.

The effects of ART and DHA alone and in combination with gemcitab on HepG2 and Hep3B were further investigated in vitro and in vivo. In addition to all four types of artemsinin derivatives, ART and DHA had the highest cytotoxic effects on hepatoma cells and despite that they had a very low degree of toxicity on normal liver cells. The basic mechanisms in these processes were inhibition of cell proliferation, G1 phase arrest and modulation of molecules in cells. Also included were apoptosis, tumor growth inhibition, and tumor gene modulation in both in vitro and in vivo.

In these activities, DHA increased the anticancer effects of gemcitabine. The researchers concluded that “ ART and DHA have a surprising anti-cancer effect on human hepatoma cells, especially on p53 status, with minimal effects on normal cells, with indications that these two derivatives are promising therapeutics for human hepatoma cancer both when used alone and when used in combination with other drugs.

Artemisinin study 2

The second study was conducted by Dr. YP Vandewyncel and his team 2014 to find therapeutic effects of artesunate on hepatocellular cancer. The main objectives of the study were evaluation and effects on tumor growth, anginogenesis, protein reactions and chemoresistance of hepatocellular carcinoma. Several types of hepatoma cells have been tested under normoxic and hypoxic conditions both in vitro and in vivo. Enzyme tests and advanced imaging techniques were used in this study. The results showed that artesunate has an effect on the vitality of cancer cells. The hypoxic state increased these effects.

Artesunat regulated vascular endothelial growth factor (essential for angionogenesis) and reduced tumor growth. The effects are further enhanced in combination with sorafenib. No hepatotoxicity was recorded during these reactions and artesunat showed no chemoresistance along with dosorubicin. These studies also concluded that artesunate is a potential drug for the treatment of hepatocellular carcinoma.

Research by DR Henry Lai

He made a very interesting study Dr. Henry Lai with his research team based on the fact that cancer cells have a larger number of transferrin receptors on the surface. Transferrin is a protein that transports iron. Transferrin, once introduced into the receptor, is introduced into the cell through a process called endocytosis. Therefore, if artemisinin is bound to transferrin, this contingent could be taken up by cancer cells leading to a high concentration in the carcinogenic cells of artemisinin introduced by transferrin.

In the cells themselves, iron would be released from transferrin. The reaction between iron and artemisinin would produce free radicals that destroy the cancerous cell from within. The researchers emphasize that this process is very selective and potent in terms of binding of artemisinin to the transferrin protein and its potency in destroying cancer cells.

A Chinese herb cures cancer

treatment of hepatocellular carcinoma

We found more facts in the article entitled “Chinese herb cures cancer” from  Dr. Robert Jay R Rowen published in 2002. According to this article, a team of scientists from Vietnam recorded a successful long-term cure in about 60% of cases  (out of 400 patients) in humans where artemisinin was combined with standard cancer treatments.

During the treatment of these patients, a 47-year-old woman, who had terminal liver cancer complicated by ascites and whose life expectancy was limited to days to a maximum of weeks, was treated with artemisinin and combination therapy. She was alive for two and a half years after the therapy without any signs of illness. This event provides solid evidence that artemisinin treatment can stabilize cancer growth very effectively.

Another study was conducted in 2013  with artemisinin derivatives AD1-AD8 on in vitro liver cancer cells. It was also concluded that these compounds have the potential as anti-cancer agents and that further animal studies are needed to further improve them.

Conclusion

The conclusion from the above studies is that artemisinin has the ability to treat hepatocellular carcinoma. Various studies have followed the effect of this drug during the invasion and spread of hepatocellular carcinogenic cells. Several cancer cell lines were treated with different concentrations of artemisinin. The results of these studies indicate that the concentration depends on the inhibitory effect on metastases both in vivo and in vitro. Several biochemical mechanisms including MMP2 metalloproteinase, TIMP2, and CDC42 cell division control have led to these effects.

Because many studies and researchers have given a very strong recommendation for the use of artemisinin and its derivatives as anticancer agents in hepatoma cancer and in the effective apoptosis of cancer cells, reducing tumors and inhibiting the spread of cancer. Further combination therapies that are better than single or solo therapies are recommended. Further research in humans is necessary to accurately determine the efficacy of this compound and to identify side effects before embarking on mass production of this promising drug.