ReviewFighting fire with fire: Poisonous Chinese herbal medicine for cancer therapy
Graphical abstract
Following the rule of “fighting fire with fire”, poisonous Chinese herbal medicine (PCHM) has long been used for cancer therapy. This review provides a rational understanding of PCHM and presents a general summarization of corresponding anticancer compounds derived from PCHM.
Introduction
As the essence of Chinese traditional culture, traditional Chinese medicine (TCM) has its own philosophy, diagnosis and treatment systems. TCM believes in the oneness of man and nature, and as such, Chinese herbal medicine (CHM) derived from botanicals, minerals and animals reflect the art of utilizing natural products in fighting diseases. It is a comprehensive summation of the experiences of TCM practitioners and its development has evolved into a holistic health care system, which shows great advantages in early intervention, personalized treatment and combination therapies as well. Traditionally, 12 870 kinds of TCM resources were prescribed, among which a number of potentially poisonous CHM (PCHM) are recognized to be restrictively applied for serious diseases. Even in the Pharmacopoeia of the People's Republic of China, many poisonous herbs are routinely recorded and described as slightly toxic, toxic and highly toxic (Table 1). This arises from the fact that poisonous herbs always possess stronger activity, and TCM physicians skilled in using poisonous medicines are highly admired in history. The application of these toxicants just provides a magic power to deal with severe diseases, this process might be described as “fighting fire with fire”.
Cancer is one of the main causes of death all over the world. The World Health Organization (WHO) estimates that 84 million people would die of cancer between 2005 and 2015 (Danhier et al., 2010). Conventional cancer therapies, including surgery, chemotherapy and radiotherapy, are showing more and more limitations because of poor prognosis and serious side effects. There has been a consequent wave of complementary and alternative medicine among cancer patients in western countries, with a prevalence as high as 80% (Xu et al., 2006). Medical herbs do represent a huge and noteworthy reservoir for novel anti-cancer drug discovery. Statistics indicated that a half part of anti-cancer drugs approved internationally between the 1940s and 2006 was either natural products or their derivatives (Newman and Cragg, 2007). Moreover, although the potential use of natural products is increasingly recognized in cancer therapy, it has been estimated that only 1/5–1/6 of plant species have been properly studied for their medical applications so far (Abelson, 1990). What is more notable is that most of these marketed natural compounds (e.g., camptothecin derivatives, epipodophyllotoxin derivatives, vinca alkaloids, etc.) in cancer treatment are concentrated on the poisonous part of CHM. Following the known principle of “fighting fire with fire”, PCHM, as a special group, have been ingeniously utilized by traditional Chinese practitioners for thousands of years. Their strong therapeutic actions are utilized to deal with many serious diseases, and many inspiring experiences were accumulated in this long process. It is well known that genotoxicity remains a challenge in the extensive application of PCHM. In cancer therapy, however, genotoxicity is what precisely desired to kill cancer cells. Through a proper approach, cytotoxic and genotoxic potential of anti-cancer drugs from PCHM can produce wonderful effects in future.
With researches progress, more and more active compounds from PCHM are identified and the mechanisms are gradually elucidated. A further improvement and application of PCHM with good prospects should be brought to light, which may help to bring PCHM to frontline of the war against cancer. Herewith, we gave a comprehensive introduction on the toxicity of CHM, aiming at providing a rational understanding of toxicity of CHM and a good controlling in clinical usage. Furthermore, through illustrating several novel PCHM-derived products in our paper, more researches are drawing praise for the sake of fully exploiting the potential of PCHM in valuable cancer therapy.
Section snippets
The boundary between toxic and non-toxic
TCM follows the concept of holism, where Chinese practitioners focus on the inherent balance of body. The human body is considered as a complexly and highly interconnected system, which is in accordance with the law of nature and dynamically regulated to maintain homeostasis (Wang et al., 2009b). The occurrence of diseases was attributed to a disturbance of the inner balance, thus drugs with special nature are used to mobilize and activate the body's natural resources to recover from the
General misconceptions about the toxicity of CHM
Generally, natural products were regarded as “gentle medicines” for their inconspicuous side effects. All over the world, there are approximately 1.5 billion people trusting in the efficacy and safety of Chinese medicine (Hosbach et al., 2003). In this sense, excessive or improper use is quite common, especially through self-administration for health care purposes. In fact, there is a big misunderstanding. Most of the active constitutes are derived from the secondary metabolites of plants,
Artful application of PCHM-based on the aspects of control measures
With remarkable activities, poisonous herbs have long been used in traditional treatment for a host of diseases, especially some difficult miscellaneous diseases such as cancer. It is primarily due to the rich experiences accumulated by skilled TCM practitioners that toxic herbs were artfully utilized to achieve the goal of fighting fire with fire. In China, even some highly toxic herbs, such as Tripterygium wilfordii (Thunder god vine or Lei gong teng), Chansu (toad venom), and minerals
Novel PCHM-derived, anti-cancer natural products
At present, there are mainly four groups of plant-derived anti-cancer drugs in clinical use. They are vinca alkaloids (e.g., vinblastine and vincristine), epipodophyllotoxin derivatives (e.g., etoposide and teniposide), camptothecin derivatives (e.g., topotecan and irinotecan) and taxanes (e.g., paclitaxel) (Da Rocha et al., 2001, Efferth et al., 2007). All of these natural products are also traditionally used and recorded as poisonous herbs in TCM. Besides, there are still many other
Conclusions and prospects
TCM has played, and still plays, an important role in primary health care in China due to its magical and unique effects. “Fighting fire with fire” represents a distinctive thinking style of Chinese practitioners and this idea has set its proper position in cancer therapy. The impact of PCHM on anticancer drug discovery was enormous in the past years, it was certainly that the influence will continue since PCHM is a huge community and from which more and more promising candidates are being
Acknowledgement
This study was supported by the Research Fund of the University of Macau (MYRG 208 (Y1-L4)-ICMS11-WYT).
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These authors contributed equally to this work.