We have studied live non-malignant (MCF10A), mildly malignant (MCF7) and malignant (MDA-MB-231) breast cancer cells and human breast cancer tissue. We demonstrate the first application of Raman imaging and spectroscopy in diagnosing the role of lipid droplets in cell line cultures that closely mimic an in vivo environment of various stages in human breast cancer tissue. We have analyzed the composition of the lipid droplets in non-malignant and malignant human breast epithelial cell lines and discussed the potential of lipid droplets as a prognostic marker in breast cancer. To identify any difference in the lipid droplet-associated biochemistry and to correlate it with different stages of breast cancer, the PCA method was employed. The chemical composition of lipids and proteins, both in the cell line models and in human breast tissue has been analyzed. The paper shows the alterations in lipid metabolism that have been reported in cancer, at both the cellular and tissue levels, and discusses how they contribute to the different aspects of tumourigenesis.

The hallmarks of carcinogenesis are aberrations in gene expression and protein function caused by both genetic and epigenetic modifications. Epigenetics refers to the changes in gene expression programming that alter the phenotype in the absence of a change in DNA sequence. Epigenetic modifications, which include amongst others DNA methylation, covalent modifications of histone tails and regulation by non-coding RNAs, play a significant role in normal development and genome stability. The changes are dynamic and serve as an adaptation mechanism to a wide variety of environmental and social factors including diet. A number of studies have provided evidence that some natural bioactive compounds found in food and herbs can modulate gene expression by targeting different elements of the epigenetic machinery. Nutrients that are components of one-carbon metabolism, such as folate, riboflavin, pyridoxine, cobalamin, choline, betaine and methionine, affect DNA methylation by regulating the levels of S-adenosyl-L-methionine, a methyl group donor, and S-adenosyl-Lhomocysteine, which is an inhibitor of enzymes catalyzing the DNA methylation reaction. Other natural compounds target histone modifications and levels of non-coding RNAs such as vitamin D, which recruits histone acetylases, or resveratrol, which activates the deacetylase sirtuin and regulates oncogenic and tumour suppressor micro-RNAs. As epigenetic abnormalities have been shown to be both causative and contributing factors in different health conditions including cancer, natural compounds that are direct or indirect regulators of the epigenome constitute an excellent approach in cancer prevention and potentially in anti-cancer therapy. AbbreviationsDNMTs, DNA methyltransferases; EGCG, (-)-epigallocatechin-3-gallate; HATs, histone acetylases; HCC, hepatocellular carcinoma; HDACs, histone deacetylases; MBDs, methyl-CpG-binding domain proteins; miRNAs, micro-RNAs; MTHF, methylenetetrahydrofolate; RA, retinoic acid; RES, resveratrol; SAH, S-adenosyl-L-homocysteine; SAM, S-adenosyl-L-methionine; UHRF1, ubiquitin-like containing PHD ring finger 1; Vit.D3, vitamin D3 IntroductionCancer initiation and progression are driven by the concurrent changes in the expression of multiple genes that occur via genetic and epigenetic alterations, leading to either activation of oncogenes and prometastatic genes, or silencing of tumour suppressor genes and to genome rearrangements and instability (Baylin et al., 2001; Widschwendter and Jones, BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2012 British Journal of Pharmacology (2012) Szyf, 2005;Stefanska et al., 2011a). Epigenetic modifications have attracted a significant amount of attention in the prevention and treatment of different illnesses, with cancer at the forefront, mainly due to their reversibility. Epigenetics refers to layers of information in addition to genetics and comprises several components such as DNA methylation, covalent histone modifications, particularly histone acetylation and me...

Aberrations in DNA methylation patterns have been reported to be involved in driving changes in the expression of numerous genes during carcinogenesis and have become promising targets for chemopreventive action of natural compounds. In the present study, we investigated the effects of all-trans retinoic acid (ATRA), vitamin D 3 and resveratrol alone and in combination with adenosine analogues, 2-chloro-

Summary. Resistant variants of the human leukaemic line K562 were developed using selection with the deoxynucleoside analogues cytosine arabinoside, 2-chlorodeoxyadenosine, udarabine and gemcitabine. The resistant lines displayed a high degree of cross resistance to all deoxynucleoside analogues, with little or no cross resistance to other agents. There was a profound accumulation defect of all nucleoside analogues in the resistant variants but no signi®cant defect in nucleoside transport in any of the variants. 5H nucleotidase activity was strongly increased and deoxycytidine kinase activity was moderately reduced in all of the resistant variants, resulting in reduced accumulation of triphosphate analogues. In addition a deletion in one of the alleles of the deoxycytidine kinase was detected in thē udarabine-resistant line. Ribonucleotide reductase activity was found to be strongly increased in the gemcitabineselected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. Free nucleotide pools were increased in the 2-chlorodeoxyadenosineselected line. There was no expression of the mdr1 gene by the resistant lines. Karyotypic analysis and FISH experiments using a 6q21 speci®c probe showed alterations in the 6(q16-q22) region which contains the 5 H -nucleotidase gene. Early events in the activation and degradation of deoxynucleoside analogues appear to constitute common mechanisms of resistance to these compounds.