Reliable Cancer Therapies

The use of standardized plant extracts for the treatment of cancer

More than 60% of all anti-cancer drugs are of natural origin or derived from natural compounds. Plants are an interesting source because of their chemically diverse constituents, the synthesis of which is often difficult or even impossible. Nevertheless, isolated compounds from plants are frequently used, but these compounds are often not sufficiently selective and cause damage to normal cells and tissues, resulting in severe side effects. The therapeutic index (the ratio between the effective dose and the toxic dose) is too small, and as a consequence the dose of the medicine cannot be increased to kill remaining or resisting tumor cells. A plant extract is a complex mixture of different, often closely related compounds that can act on different targets, making it an interesting "cocktail" of natural origin. Because of the generally low concentration of the constituents, there is low toxicity, whereas with regard to the activity, synergism is often observed. In addition, it can be a cheaper alternative compared to other expensive cancer treatments such as monoclonal antibodies.
Therefore, three different plant extracts will be investigated in this project for their possible use in the treatment of cancer.
 

1) Chelidonium majus
2) Steganotaenia araliaceae
3) Gloriosa superba

Chelidonium majus (Papaveraceae) is an herb that is widely spread in Europe and is used in folk medicine against disorders of liver and bile. It contains interesting alkaloids and both the crude extract and the constituents have already shown antitumoral activity, though the single compounds were often found too toxic for human use. Since 1991 the product Ukrain™ is commercially promoted and appears in different clinical trials. It is said to be a semi-synthetic derivative with a trimeric structure containing 1 thiophosphoric acid and 3 chelidonine molecules. However, chemical analyses rather concurred with a mixture of Chelidonium alkaloids and the trimeric structure has never been retrieved in the Ukrain™ product. The promising activity of Ukrain™ on the one hand and the ambiguous content of this expensive medicine on the other hand, are reasons to investigate and evaluate Chelidonium majus extract.

Steganotaenia araliacea (Apiaceae) is known in African traditional medicine for its antitumoral activity. It contains cytostatic lignans of which steganacine is the most promising compound. It has already been thoroughly studied and compared to podophyllotoxin (a cytostatic lignan of which the anticancer drug etoposide was derived). Because of the traditional use of this plant and the research already performed on the main constituent steganacine, Steganotaenia araliacea extract is a good candidate for this study.

Gloriosa superba (Liliaceae) is used in traditional medicine in India (Ayurveda) for several purposes, such as the treatment of gout, snake bites, intestinal worms, etc. In South-Africa it is said to have anticancer activity, though high doses are known to be toxic. The tubers contain colchicine, a well-known medicine against gout. The seeds of this plant even serve as a commercial source for this drug. Gloriosa superba contains other, very similar alkaloids such as gloriosine, demethylcolchicine and the glucoside colchicoside. By using this mixture containing derivatives in low concentrations, the plant preparation can have several benefits compared to the pure compound. Some of the related compounds can have a better therapeutic index (thus less toxic). On the other hand, the extract contains prodrugs, such as colchicoside, that are less toxic and have a better solubility. These are the reasons why Gloriosa superba extract is selected as a potential anticancer medicine.

The research deals with:
(1) phytochemical characterization, i.e. isolation and identification of the active constituents using chromatographic and spectroscopic techniques;
(2) analytical method development and validation in order to produce standardized plant extracts with reproducible quality;
(3) pre-clinical studies to determine the efficacy and toxicity of the plant extracts and their components (in vitro and in vivo).

Parts 1 and 2 (above) are currently being performed in the laboratory of Pharmacognosy and Pharmaceutical Analysis and part 3 will be performed in the laboratory of Cancer Research and Clinical Oncology, both from the University of Antwerp (UA). The project is supported by an IWT Doctoral Scholarship.

The final goal is to prepare one or more of these plant extracts (depending on the preclinical results) for clinical trials. Therefore, Prof. M. Peeters from the university hospital of Antwerp (UZA) provides advice for the project.