Traditional Medicinals and Cancer

By: Lynn Stephenson, Product Specialist, Sigma® Life Science and Chloe McClanahan, Product Manager, Sigma Life Science, Biofiles Vol. 8, No. 6

Traditional Chinese Medicine (TCM) is a healing art that has been practiced for thousands of years. The practice of TCM is a holistic approach that includes the use of herbal preparations, acupuncture, and dietary therapy with the goal of returning the body to a healthy, balanced state. Under TCM theory, cancer is a disease that arises due to disturbances in the body from both endogenous physical conditions and exogenous pathogenic stresses and the goal of therapy is on restoring the body’s natural defenses1. Herbal preparations are a common component of TCM and there has been an increase in research interest in understanding the molecular mechanisms by which many of these medicinal herbs elicit their effects with the hope that these can be translated into new therapies. Many commonly used drugs in cancer treatment, for example paclitaxel and camptothecin, are derived from natural sources and TCM, with over 7,000 herbs, represents a rich source of potential new compounds2.

Recent work has begun to unravel the molecular mechanisms by which many TCM-derived compounds elicit their antitumor effects. The targets of these compounds tend to broadly fall into three categories, those targeting topoisomerases, those inducing apoptosis, and those disrupting oncogenic signaling pathways1.  Resistance to apoptosis is a common hallmark of cancer cells3 and induction of apoptosis is a common mechanistic endpoint of many effective anti-cancer therapies. Within the TCM compounds that have been isolated,  induction of apoptosis is the most common mechanism by which TCM-derived compounds elicit their anti-tumor effects1,4. For example, Cantharidin, isolated from the Chinese Blister beetle, has been reported to induce apoptosis in a variety of tumor cell lines including human leukemic, colon cancer, and human hepatoma, most likely through inhibition of protein phosphatase 2A (PP2A)5. Of the compounds studied to date that have shown anti-tumor effects, the vast majority induce apoptosis, primarily through the regulation of apoptotic signaling molecules1. These studies are helping to validate that many of the compounds used in TCM have true biological effects that may be translated into new therapeutics.

The materia medica of traditional medicinal systems represent a rich source of time-tested therapeutics and thus, an excellent source of potential new bioactive molecules. In particular, pharmaceutical companies have been investigating compounds isolated from medicinal herbs as a potential source of new lead compounds for drug discovery. TCM has been the source of many new drugs including artemisinin, camptothecin, triptolizde, and ephedrine6. The discovery of camptothecin highlights the tremendous potential that can be gained from research into plant compounds. Camptothecin, a cytotoxic topoisomerase inhibitor, is found in the Chinese happy tree (Camptotheca acuminate) which was of research interest because it has been used in TCM formulations for thousands of years. This discovery resulted from a cross-discipline research program between botanists at the USDA and chemists at the National Cancer Institute (NCI)  during the 1960s7. Camptothecin analogs were eventually made available as pharmaceuticals for the treatment of various cancer types.

During the 1960s, Research Triangle Institute developed innovative methods for plant extract fractionation and subsequent in vitro cytotoxicity testing of isolated compounds7. These methods, derived from a reductionist research approach, were critical to camptothecin discovery but most TCM formulas are based on the synergistic effects of multiple components, each containing many potentially bioactive ingredients. Recent research is indicating that a systems biology or network biology approach may be a better course for understanding the combinatorial effects of compounds within a TCM preparation. Advances in instrumentation are enabling researchers to integrate chemical identification, pharmacological, metabolomics, and bioinformatics data from herbal preparations. Analysts at the University of Copenhagen used a new platform that combines HPLC and NMR chemical identification with a metabolomics-based radical scavenging assay to determine both the chemical and pharmacological fingerprint of a willow bark extract. Willow bark has been applied historically in TCM as an analgesic but it also exhibits anti-proliferative activity and induces apoptosis in vitro8-9.

Sigma offers a unique portfolio of high-purity secondary metabolites derived from Traditional Chinese Medicinal herbs that may be applied individually in cancer screening assays or as benchmarks in complex biological network analysis.

 


 

Jars of ginseng root typically seen in a TCM pharmacy. Ginseng extracts contain a class of bioactive saponins termed ginsenosides that have been shown to reverse multi-drug resistance in chemotherapy research.

 


 

The fruit hull from mangosteens are used in TCM as an anti-inflammatory treatment. γ-Mangostin and α-Mangostin (Sigma Cat. Nos. M6824 and M3824), xanthones isolated from mangosteen, have been shown to have anti-cancer activity, specifically cytotoxicity, apoptosis, and anti-tumorigenicity.

 


 

Curcumin (Sigma Cat. No. C1386) is a natural phenolic compound isolated from the medicinal plant turmeric. It has been studied as a potential chemotherapeutic.

 


Materials

     

 References

  1. Hsiao, W. L. W. and Liu, L. The Role of Traditional Chinese Herbal Medicines in Cancer Therapy - from TCM Theory to Mechanistic Insights. Planta Med, 76, 1118-1131 (2010).
  2. Parry, J. Taking a New Look at an Ancient Tradition. The Scientist 19, (2005).
  3. 3. Hanahan, D. and Weinberg, W.  Hallmarks of Cancer: The Next Generation. Cell, 144, 646- 674 (2011).
  4. Parekh, H.S. et al.  A New Dawn for the Use of Traditional Chinese Medicine in Cancer Therapy. Mol. Cancer, 8, 21 (2009)
  5. Youns, M. et al. Traditional Chinese Medicines (TCMs) for Molecular Targeted Therapies of Tumours.  Curr. Drug Disc Technol. 7, 2-12 (2010).
  6. Li, X.-J., et al. Chemoinformatics Approaches for Traditional Chinese Medicine Research and Case Application in Anticancer Drug Discovery. Curr. Drug Disc Technol. 7, 22-31, (2010).
  7. Ginsberg, J. The Discovery of Capmptothecin and Taxol. In American Chemical Society Education. Retrieved November 5, 2012 from
  8. Afnolet, S. et al. Comprehensive analysis of commercial willow bark extracts by new technology platform: Combined use of metabolomics, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy and high-resolution radical scavenging assay. J. Chromatogr. 1262, 130-137, (2012).
  9. Hostanka, K. et al. Willow Bark Extract (BNO1455) and its Fractions Suppress Growth and Induce Apoptosis in Human Colon and Lung Cancer Cells. Cancer Detect. Prev. 31, 129-139 (2007).

 

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