Dietary restriction: could it be considered as speed bump on tumor progression road?

Abstract

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long-and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models.However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans

“…Previous studies also showed that tumor suppressor genes, daf-16/ Foxo, daf-18/Pten, and lin-35/Rb are required for promoting C. elegans starvation survival (Baugh and Sternberg 2006;Cui et al 2013). Starvation or fasting has recently been investigated in cancer therapy (Naveed et al 2014;Cangemi et al 2016), as tumor cells are thought to be more susceptible to starvation due to the Warburg effect (Iansante et al 2015). Results from this study and previous work using C. elegans may suggest that cancer cells, that commonly harbor mutations in tumor suppressor genes, are highly sensitive to starvation stress.…”

The nucleolus, an ally, and an enemy of cancer cells

“…Consequently, cancer cells are selectively killed, mainly by autophagy. On the contrary, normal starved cells halt cell cycle through insulin-like growth factor-1 and shift energy deficiency towards survival (Buono and Longo 2018; Cangemi et al 2016; Lee et al 2010). Although reports concerning therapeutic effects directly connecting diet and ribosome production are lacking, relationship between these two seems to be plausible.…”

Effects of Dietary Restriction on Cancer Development and Progression

“…It is clear that beneficial effects mediated by fasting, in particular by CR, do not involve a single gene, a pathway or a unique molecular mechanism. The benefits are due to the negative regulation of nutrient-signaling pathways, including insulin-like growth factor 1 (IGF-1) pathway and its effector extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K), which are known to modulate important proliferation pathways (Cangemi et al 2016). Furthermore, it is well known that genomic instability is a distinctive feature of cancer, and CR tumor response seems to play a key role for the maintenance of genomic integrity (Robertson and Mitchell 2013;Duan et al 2017).…”

“…This protein is able to modulate the expression of genes involved in oxidative metabolism, stress resistance, and longevity (Cangemi et al 2016). It has been observed that DR-sensitive cells show a decrease in AKT cytoplasmic levels.…”

“…DR-induced autophagy is activated by poly (ADPribose) polymerase 1 (PARP-1), a nuclear enzyme induced by DNA damage. ROS (reactive oxygen species) production under DR conditions causes DNA damage, which determines PARP-1 activation and fasting-induced autophagy (Cangemi et al 2016). ROS induce different types of DNA damage, including single-strand breaks (SSBs), double-strand breaks (DSBs), and ionized DNA nucleotides.…”