Cancer Therapy with Natural Products and Medicinal Plants

A review of the drug development process during the past half century clearly shows that drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. In fact, about one quarter of all drugs in modern pharmacopeia derive from plants. If semisynthetic derivatives of natural compounds or drugs mimicking pharmacophores from natural products are included into this group, the numbers are even higher.

Phytotherapy represents the oldest form of therapy worldwide. It is estimated that two thirds of the world population resort to medicinal plants derived from folk medicines. Traditional medicines are cheaper than drugs from pharmaceutical companies. In many cases, medicinal plants from folk medicine are the only health care. This is especially true for rural areas. More than 21 000 plant species are used worldwide in herbal medicines as compiled by the World Health Organization.

Cancer still belongs to the second leading cause of death in industrialized countries. The fate of many cancer patients, for whom cure of their disease is not a reality, is becoming ever more of an issue. As repeatedly shown by the National Cancer Institute, USA, more than two thirds of the anticancer drugs approved between the 1940s and 2006 are either natural products or were developed based on the knowledge gained from natural products. Arguably, about three quarters of the plant-derived drugs in clinical use today came to the attention of pharmaceutical companies because of their use in traditional medicine. It comes as no surprise that natural products belong to the major players in cancer research, since a considerable portion of antitumor agents currently used in the clinic are of natural origin. Drugs of different classes are part of the armatorium to fight the war against cancer, e.g., Vinca alkaloids (vincristine, vinblastine, vindesine, vinorelbine), taxanes (paclitaxel, docetaxel), epipodophyllotoxines (etoposide, teniposide), camptothecin and its derivatives (topothecan, irinothecan), anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin), and others. Over the past years, there was a major shift in the development of cancer drugs, from screening of cytotoxic drugs to the development of molecularly targeted drugs. The conceptual idea is that the knowledge of the action mechanism(s) of a drug provides a better approach to reach improved clinical results on the basis of the patients' molecular characteristics. The complexity of this task requires the interaction of scientists from different fields.

There are unprecedented efforts to uncover new treatments, and the knowledge on cancer has increased dramatically over the past three decades ([Fig. 1]). In this context, natural product research and herbal therapies have become thriving fields of research. A comprehensive survey of published papers from 1979 to 2009 shows that all research fields related to cancer treatment were growing over time, which reflects generally increasing research efforts worldwide ([Fig. 1 A] and [B]). A closer look to natural product and herbal therapy research, however, revealed that this area seems to grow more in terms of annual publication output since the year 2000 than the other fields analyzed ([Fig. 1 B]). It has to be taken into account that the total paper output is considerably smaller in natural product research (one order of magnitude) and herbal therapy (three orders of magnitude) compared to pharmacological or cancer research, but despite being small and specialized research areas, the increase rates over the years were considerable. The number of annually published papers in herbal therapy research increased 49-fold during the past three decades and the one of papers on herbal therapy in the context of cancer treatment even 101-fold ([Fig. 1 C]), indicating that this small research topic took a booming development. Even during the past decade, papers on herbal therapy and cancer increased most among all research topics analyzed (3.6-fold; [Fig. 1 D]), and herbal therapy and natural product research in general had higher fold increases in terms of annually published papers than the established research disciplines pharmacology or cancer. These facts and figures illustrate that the present special issue of Planta Medica focuses on a hot topic in research.

Fig. 1 A to D Survey of literature deposited in the PubMed database from 1979 to 2009 with the keywords (A) pharmacology, cancer, drug, and drug and cancer; (B) natural product, natural product and cancer, herbal therapy, and herbal therapy and cancer. The fold increase of published papers during the past three decades (C) and during the past decade (D) is shown.

For this special issue, I was fortunate to gather a panel of reputed experts from different fields working on innovative small molecules of natural origin:

Qing-Xi Yue, Xuan Liu, and De-An Guo (Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai, China): Microtubule-binding natural products for cancer therapy. Sahdeo Prasad, Kannokarn Phromnoi, Vivek R. Yadav, Madan M. Chaturvedi, and Bharat B. Aggarwal (Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA): Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer. Sachiko Tsukamoto (Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan): Inhibition of the ubiquitin-proteasome system by natural products for cancer therapy. Simone Fulda (University Children's Hospital, Ulm, Germany): Modulation of apoptosis by natural products for cancer therapy. Alan L. Harvey and Ian A. Cree (Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK, and Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth, UK): High throughput screening of natural products for cancer therapy. Marcy J. Balunas and A. Douglas Kinghorn (Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA, and Ohio State University, OH, USA): Natural product compounds with aromatase activity: an update. Rob Verpoorte, Young H. Choi, and Hye Kyong Kim (Leiden University, Leiden, Netherlands): Metabolomics: a tool for anticancer lead-finding from natural products. Kandan Aravindaram and Ning-Sun Yang (Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan): Anti-inflammatory natural products for cancer therapy. W. L. Wendy Hsiao and Liang Liu (Department of Biomedical Sciences and School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China): Recent development of traditional Chinese herbal medicines in cancer therapy – from the TCM theory to the basic research. Mandeep Virk Timothy Nagy and Steven Barnes; (Department of Nutrition Sciences and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA): Role of phytoestrogens in cancer therapy. Thomas Efferth (Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany): Personalized cancer medicine: from molecular diagnostics to targeted therapy with natural products. Lina Pinto-Garcia, Thomas Efferth, Amada Torres, Jörg Hoheisel, and Mahmoud Youns (German Cancer Research Center, Heidelberg, Germany, and Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany): Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells.