Manuka honey in combination with 5-Fluorouracil decreases physical parameters of colonspheres enriched with cancer stem-like cells and reduces their resistance to apoptosis.

The aim of the present work was to evaluate the in vitro effect of Manuka honey and its combination with 5-Fu, the most common drug used in the treatment of colon cancer, on the morphological and physical parameters of colonspheres enriched with cancer stem-like cells deriving from HCT-116 colon adenocarcinoma cell line and on the apoptosis rate. Manuka honey, alone and more in combination with 5-Fu, reduced the weight, the diameter and mass density of the spheroids and induced apoptosis through the downregulation of many apoptosis inhibitors, including IAPs (Livin, Survivin, XIAP), IGFs (IGF-I, IGF-II and IGF-IR) and HSPs (HSP-27, HSP-60 and HSP-70). These results led to a reduction in the survival ability of cancer stem-like cells, as well as to a chemosensitizing effect of honey towards 5-Fu, considering that apoptosis resistance is one of the main causes of cancer stem-like cells chemoresistance.

The Molecular Basis of Different Approaches for the Study of Cancer Stem Cells and the Advantages and Disadvantages of a Three-Dimensional Culture.

Cancer stem cells (CSCs) are a rare tumor subpopulation with high differentiation, proliferative and tumorigenic potential compared to the remaining tumor population. CSCs were first discovered by Bonnet and Dick in 1997 in acute myeloid leukemia. The identification and isolation of these cells in this pioneering study were carried out through the flow cytometry, exploiting the presence of specific cell surface molecular markers (CD34+/CD38-). In the following years, different strategies and projects have been developed for the study of CSCs, which are basically divided into surface markers assays and functional assays; some of these techniques also allow working with a cellular model that better mimics the tumor architecture. The purpose of this mini review is to summarize and briefly describe all the current methods used for the identification, isolation and enrichment of CSCs, describing, where possible, the molecular basis, the advantages and disadvantages of each technique with a particular focus on those that offer a three-dimensional culture.

Nutritional Value and Preventive Role of Nigella sativa L. and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies.

In recent times, scientific attention has been paid to different foods and their bioactive components for the ability to inhibit the onset and progress of different types of cancer. Nigella sativa extract, powder and seed oil and its main components, thymoquinone and α-hederin, have showed potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors, through the modulation of various molecular signaling pathways. Herein, the purpose of this review was to highlight the anticancer activity of Nigella sativa and it constitutes, focusing on different in vitro, in vivo and clinical studies and projects, in order to underline their antiproliferative, proapoptotic, cytotoxic and antimetastatic effects. Particular attention has been also given to the synergistic effect of Nigella sativa and it constitutes with chemotherapeutic drugs, and to the synthesized analogs of thymoquinone that seem to enhance the chemo-sensitizing potential. This review could be a useful step towards new research on N. sativa and cancer, to include this plant in the dietary treatments in support to conventional therapies, for the best achievement of therapeutic goals.