Towards New Anticancer Strategies by Targeting Cancer Stem Cells with Phytochemical Compounds

Abstract

Cancer stem cells (CSCs) are believed to be responsible for tumor initiation and development, metastasis and resistance to radio-therapy and a priori to numerous natural or synthetic chemical compounds. A large body of observations support now the 100 year old hypothesis which predicted a clonal genetic background of the heterogeneous cell population found in a tumor outgrowth [Paget, 1889]. Accordingly, since Dick's laboratory pioneering work in 1994 [Lapidot et al., 1994], growing realizations suggest that CSCs arise from embryonic, fetal or adult stem cells (SCs) or closely related dedifferentiated descendants. Interestingly, the concept that CSCs give rise to the bulk cancer cells is in accordance with the germ theory of disease developed by Koch in the 19th century [Garcion et al., 2009]. This theory points out that any disease has a unique causative agent. Although Koch’s dogma suggests that tumors should arise from CSCs, it must also be borne in mind that their descendant cancer cells can generated dedifferentiated cells with a parental phenotype and therefore can be involved in the outburst of a secondary cancer. On the basis of epidemiological data, it has been recurrently reported that diet rich in fruits and vegetables has cancer-protective properties; this suggests that plant-derived compounds are able to restrict the expansion of CSCs and even to kill them. The chemotherapeutic benefits of different natural or synthetic phytochemical agents on cancer cells are well documented. However their effects on CSCs are poorly understood, to a large extent because on the absence of well characterized experimental models. The objective of this chapter is therefore to recapitulate some aspects of the biology of CSCs and to propose different cellular tools and molecular preys for thorough pharmacological studies on CSCs, on the basis of the most recent data concerning the stemness factor Oct4. After reviewing known effects of specific phytochemicals on CSCs, we will focus on related promising strategies which could target the Achilles’ heel of CSCs, in particular those harboring a selective sensitivity to oxidative stress and/or present in weakly differentiated Oct-4 expressing cancers.