The effect of naturally-occurring dietary compounds on Cancer Stem Cells

The first use of chemotherapeutic agents to treat cancer was in the early twentieth century, which became the basis of discovery and development of most current anti-cancer drugs. Although a large majority of chemotherapeutic drugs can considerably shrink tumor sizes, they often fail to eradicate tumors. The cancer may eventually develop drug resistance and recurrence.In recent years, a great deal of research has demonstrated the existence of cancer stem cells (CSCs) or tumor-initiating cells (TICs) in several human cancers. However, most currently available therapeutic approaches, including chemotherapy and radiotherapy, lack the ability to effectively kill these CSCs. Therefore, this CSC population has become a target for cancer prevention and therapy.The CSC theory asserts that many types of cancer are initiated from and maintained by a minor population of tumorigenic cells that are capable of continuous self-renewal and differentiation. This cell population undergoes unlimited proliferation and gives rise to differentiated cells, developing new tumors phenotypically recapitulating the original tumors. In addition, recent studies indicate that CSCs may be responsible for tumor relapse and resistance to therapy. So far, several major pathways including Wnt/β-catenin, Hedgehog, and Notch have been identified to play pivotal roles in CSC self-renewal.It is suggested that targeting CSCs could be achieved by several strategies including sensitizing them to chemotherapeutic agents, induction of differentiation, and inhibition of self-renewal signaling.A plethora of naturally-occurring dietary compounds have been proven to be promising chemoprevention agents against various types of cancer. A number of studies have found that some dietary compounds including Curcumin, Sulforaphane, Soy Isoflavone, Epigallocatechin-3-Gallate, Resveratrol, Lycopene, Piperine and Vitamin D3 can directly or indirectly affect CSC self-renewal pathways. These naturally-occurring dietary compounds are advantageous in several aspects as chemoprevention agents: (1) they are present in commonly consumed food, which is readily available to most people in daily life; (2) they usually have very low or no toxicity, in contrast to most chemotherapy drugs; (3) many of these compounds have shown potential as an adjunct to chemotherapy drugs in some clinical trials. Investigating the efficacy of the dietary compounds against CSCs will provide rationale for preclinical and clinical evaluation of these compounds or potentially their native food extracts for chemoprevention of CSCs. These studies will eventually enable us to discover more effective strategies for cancer treatment to reduce cancer resistance and recurrence and to improve patient survival.