Cancer Stem Cells and Chinese Herbal Medicine
The deepening of our understanding of normal biology has made it clear that stem cells have a critical role not only in the generation of complex multicellular organisms, but also in the development of tumours. Recent findings support the concept that cells with the properties of stem cells are integral to the development and perpetuation of several forms of human cancer (Jordan, Guzman & Noble 2006).
Cancer stem cells (CSCs) are cancer cells (found within tumours or haematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumourigenic (tumour-forming), perhaps in contrast to other non-tumourigenic cancer cells. CSCs may generate tumours through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumours as a distinct population and cause relapse and metastasis by giving rise to new tumours. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease (Dalerba, Cho, & Clarke 2007).
The existence of CSCs is a subject of debate within medical research, because many studies have not been successful in discovering the similarities and differences between normal tissue stem cells and cancer stem cells (Rosen & Jordan 2009). Cancer cells must be capable of continuous proliferation and self-renewal in order to retain the many mutations required for carcinogenesis, and to sustain the growth of a tumour since differentiated cells cannot divide indefinitely (constrained by the Hayflick Limit). However, it is debated whether such cells represent a minority. If most cells of the tumour are endowed with stem cell properties, there is no incentive to focus on a specific sub population. There is also debate on the cell of origin of CSCs – whether they originate from stem cells that have lost the ability to regulate proliferation, or from more differentiated population of progenitor cells that have acquired abilities to self-renew (Li et al., 2007).
Dalerba, P., Cho, R.W. & Clarke, M.F. Cancer Stem Cells: Models and Concepts. Annual Review of Medicine. (2007) Vol. 58: Pp. 267-84. doi:10.1146/annurev.med.58.062105.204854
Gupta, P.B., Chaffer, C.L. & Weinberg, R.A. (2009). “Cancer stem cells: mirage or reality?”. Nature Medicine. 15 (9): 1010–2. doi:10.1038/nm0909-1010
Jordan, C.T., Guzman, M.L. & Noble, M. New England Journal of Medicine. Mechanisms of Disease; Cancer Stem Cells. 355;12 www.nejm.org september 21, 2006
Li, F., Tiede, B., Massagué, J. & Kang, Yb. Beyond tumourigenesis: cancer stem cells in metastasis. Cell Research (2007) 17: Pp. 3–14. doi: 10.1038/sj.cr.7310118
Rosen, J.M. & Jordan, C.T. The Increasing Complexity of the Cancer Stem Cell Paradigm. Science. (2009) Vol. 324. no. 5935, Pp. 1670 – 73 DOI: 10.1126/science.1171837
Figure 1. Examples of Stem Cells Found in Adult Somatic Tissues; Neural stem cells generate cells in the central nervous system (Panel A). Haematopoietic stem cells generate mature blood cells (Panel B). Mammary stem cells generate breast tissue (Panel C).
Research and Theory in Chinese Herbal Medicine
1. Progress of studies on tumour stem cell and anti-cancer treatment by nourishing Shen essence and qi
The tumour stem cells (TSC) existing in the tumour plays a crucial role in carcinogenesis though very few in number. It is a special kind of stem cells with highly proliferative and self-regenerative cap ability to maintain its number stable and generate tumour. Therefore, the radical treatment of tumour should focus on TSC. TSC are derived from adult stem cells. According to TCM theory, normal stem cells belong to the category of Shen essence and qi, and patients suffering from malignant tumour always manifest as the syndrome of essence and qi deficiency, so nourishing Shen essence and qi should be of great importance for treatment of tumour.
—Zheng Zhan, Xu Zhenye. Zhong Guo Zhong Xi Yi Jie He Za Zhi. 2007 Jan;27(1):89-92.
2. Interference of Chinese herbs in different treating methods on lung adenocarcinoma stem cell and its mechanism.
The cancer stem cell theory was reviewed in the article. Based on the theory that BASCs (bronchioalveolar stem cells) is believed to be the initiating cells of lung adenocarcinoma and can produce this type of cancer, the aetiology and pathogenesis of lung cancer in TCM were analysed. Evidences showed that TCM had significant effects on various aspects of lung cancer including occurrence, growing, metastasis, recurrence and drug resistance., but there was no evaluation and mechanism research on the interference of TCM on cancer stem cells in all literatures on TCM preventing and treating tumours within last five years. As isolating method and biological characteristics of lung adenocarcinoma stem cell were quite clear, it’s theoretically and practically important to observe the effects of Chinese herbs in different treating methods such as Heat-clearing & Toxic-removing, qi-invigorating, yin-nourishing, Blood-activating & stasis-resolving and Phlegm-resolving on basic behaviours of lung adenocarcinoma stem cell.
—Hu Zuowei. Hu Bei Min Zu Xue Yuan Xue Bao: Yi Xue Ban. 2008; 25(3): 70-72.
3. Tumour stem cells may be the final target of traditional Chinese medicine in preventing cancer recurrence and metastasis
The recurrence and metastasis of tumour are the main reasons for the failure in malignant tumour treatments, searching for the best target to prevent the tumour recurrence and metastasis is the focus of tumour research. Research showed that tumour stem cells are the vital factor of malignant tumour recurrence and metastasis, there is no method of target regulating the function of tumour stem cells now. Traditional Chinese Medicine have played a good role in preventing tumour recurrence and metastasis according to the previous studies, so we can suppose that tumour stem cells may be the final target of TCM in preventing tumour recurrence and metastasis. To expand the effect and study the mechanism of action we should introduce the tumour stem cells into the study of TCM in treating malignant tumour.
—Zhang Ying, Lin Hongsheng. Zhong Guo Zhong Xi Yi Jie He Za Zhi. 2009 May;29(5):461-463.
4. Discussion on the new mechanism of treating primary liver cancer with Spleen and Kidney theory.
Inspired by the Liver cancer stem cell theory in modern medicine, it’s put forward that deficiency of the Spleen and Kidney is the basic syndrome of liver cancer, and Spleen-strengthening and Kidney-invigorating method is the permanent cure for primary liver cancer.
—Tian Mingtao, Bao Xinhua. Zhong Guo Zhong Yi Yao Xian Dai Yuan Cheng Jiao Yu. 2009; 7(6): 11-12.