Colorectal cancer (CRC) invasion within the large intestine wall results in the replacement of normal tissue architecture by tumour mass. Cancer cells digest the extracellular matrix (ECM) by the release of proteolytic enzymes. The disintegration of matrix ground substance activates several deposited growth factors which stimulate cell proliferation. Stromal (mainly fibroblasts), immune and cancer cells dominate in this area and become involved in a network of multimodal interactions which significantly induce proliferation of colon cancer cells, inhibit their apoptosis and promote their spreading within the local tumour microenvironment. Cancer invasion destroys nerve fibres and neurons of the local enteric nervous system (ENS) and induces subsequent atrophy of the submucosal and myenteric plexuses in areas adjacent to the cancer boundary. Interestingly, the reduction of plexuses’ size is accompanied by the increased number of galanin-immunoreactive neurons and increased galanin content in parts of the colon located close to the tumour. Galanin, a neuroprotective peptide, may inhibit the extrinsic pathway of apoptosis and in this way promote cancer cell survival. The possible role of acetylcholine and some ENS neuropeptides was also discussed. Invasion of cancer cells spreads along nerve fibres with the involvement of locally-released neutrophins which promote, via their specific receptors, cancer cell proliferation and pro-survival signalling pathways. Thus, during CRC development cancer cells and neurons of the ENS release many neurotransmitters/neuropeptides which affect key cellular signalling pathways promoting cancer cell proliferation and pro-survival phenotype. The multiple interactions between ENS neurons, cancer cells and other cell types present in the colon wall increase cancer cell invasiveness and have a negative impact on the course of CRC.

The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The mechanism of autophagy depends on the genetic context, tumor stage and type, tumor microenvironment, or clinical therapy used. Autophagy also plays an important role in cell death as well as in the induction of chemoresistance of cancer cells. The following review describes the extensive autophagic cell death in relation to dietary polyphenols and cancer disease. The review documents increasing use of polyphenolic compounds in cancer prevention, or as agents supporting oncological treatment. Polyphenols are organic chemicals that exhibit antioxidant, anti-inflammatory, anti-angiogenic, and immunomodulating properties, and can also initiate the process of apoptosis. In addition, polyphenols reduce oxidative stress and protect against reactive oxygen species. This review presents in vitro and in vivo studies in animal models with the use of polyphenolic compounds such as epigallocatechin-3-gallate (EGCG), oleuropein, punicalgin, apigenin, resveratrol, pterostilbene, or curcumin and their importance in the modulation of autophagy-induced death of cancer cells.

Background: Regulatory mechanisms of metabolic homeostasis undergo important alterations during ageing. The age-related changes become often evident only during stimulation of basic functions that occurs, e.g. during fasting and refeeding which represent natural challenge to energy metabolism. Objective: To determine the effect of short-term fasting and subsequent refeeding on serum levels of key hormones and metabolites in young adult 5- and 24-month-old male Wistar rats. Methods: Control rats were fed ad libitum. Animals were fasted for 48 h or fasted and refed for 24 h. Metabolite serum concentrations were measured by standard methods. Leptin and insulin were determined by rat-specific RIA, and adiponectin serum levels by mouse/rat–specific ELISA. Results: (1) Control serum levels of key metabolites and hormones were similar in both age groups except for increased triglycerides (TG) in old fed rats. (2) Fasting caused a significant decrease of leptin, insulin, glucose, and TG serum levels in both age groups, and an increase of free fatty acids (FFA) concentration, however, only in young animals. (3) Upon refeeding serum glucose, TG and insulin reversed to control levels in both age groups, however, FFA concentration decreased to control values only in young rats. (4) In contrast to young animals, refeeding of old rats did not increase serum leptin concentration to control level. (5) Neither fasting nor refeeding changed adiponectin serum levels in both age groups. Conclusion: Aging suppresses leptin secretion and metabolism of FFA during refeeding that follows short-term starvation. In old rats serum levels of FFA are refractive to the alterations induced by fasting/refeeding in young ones.