Dietary Phytochemicals Target Cancer Stem Cells for Cancer Chemoprevention

Abstract

Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Cancer progression ends in tumor metastasis to distant sites, and metastasis is the major reason for cancer patient deaths. Recent experimental evidence suggests the pivotal role of cancer stem cells. A tumor is heterogeneous and composed of different cell types. The cancer stem cells in the tumor have the capacity both to self-renew and differentiate to sustain the tumor. Features of cancer stem cells are described in this review, with an emphasis on the role that dietary phytochemicals may play in cancer chemoprevention. Ingredients in the diet can inhibit cancer cells and cancer stem cells. These compounds include curcumin from curry, epigallocatechin gallate from green tea, resveratrol from red wine, genistein from soy, sulforaphane from broccoli, and many others. Current research findings advocate the beneficial effects towards cancer chemoprevention via uptake of a combination of different dietary phytochemicals.

Targeting cancer stem cells with dietary phytochemical - Repositioned drug combinations

“…Different models are available: athymic nude mice, non-obese diabetic/ severe combined immunodeficiency (NOD/SCID) mice, and NOD/SCID interleukin-2 receptor gamma chain null (Il2rg −/− ) (NSG) mice. The abundance of CSCs in a tumor sample can be estimated as the xenotransplantation yield, which confirms the presence of CSCs by limiting dilution analysis [6].…”

“…The "side population" (SP) assay identifies CSCs apart from the main population of cancer cells in flow cytometry, by their fast expulsion of a fluorescent dye (Hoechst 33342). However, cell surface markers for CSC selection are also present in normal stem cells and other cell types, they are not unique to CSCs [6]. Both SP and ALDH selections were originally developed for hematopoietic stem cells (HSCs) and then adapted to CSCs.…”

“…Spheroids mimic the three-dimensional nature of tumors with limited oxygen available to the internal cells. This hypoxic condition favors expression of pluripotency maintaining transcription factors, thus promoting the differentiation to CSCs and facilitating the state of "stemness" [6]. Spheroids can form secondary and tertiary spheres in subsequent cultures.…”

“…The first yielded cyclopamine from the plant corn lily Veratrum californicum; it targets glioblastoma CSCs via the Hedgehog pathway but can act as a teratogen that causes cyclopia. The second yielded salinomycin from the bacterium Streptomyces albus; it is toxic to humans so its use is confined to the poultry industry, as a coccidiostat for treating a parasitic protozoan disease [6]. For clinical uses, medicinal chemists must modify to remove teratogenicity or toxicity.…”

“…Examples are paclitaxel for several cancer types and imatinib (tyrosine kinase inhibitor) for chronic myelogenous leukemia (CML). However, CSCs are resistant to these anti-cancer drugs [6]. A curative cancer therapy must acknowledge CSC plasticity and their complete elimination.…”