The Multifaceted Role of Heme in Cancer

Abstract

Heme, an iron-containing porphyrin, is of vital importance for cells due to its involvement in several biological processes, including oxygen transport, energy production and drug metabolism. Besides these vital functions, heme also bears toxic properties and, therefore, the amount of heme inside the cells must be tightly regulated. Similarly, heme intake from dietary sources is strictly controlled to meet body requirements. The multifaceted nature of heme renders it a best candidate molecule exploited/controlled by tumor cells in order to modulate their energetic metabolism, to interact with the microenvironment and to sustain proliferation and survival. The present review summarizes the literature on heme and cancer, emphasizing the importance to consider heme as a prominent player in different aspects of tumor onset and progression.

Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study

“…Processed meat on the other hand has less valuable nutrients and can be high in fat and salt”. Current knowledge on meat cancer risk had been partially explained by Western diet rich in energy and fat, or by various compounds in meat [ 5 ], including heme [ 49 ]. While this iron-containing porphyrin functions in vital biological processes (i.e., oxygen transport, energy production, drug metabolism), heme can be toxic at high levels.…”

“…While this iron-containing porphyrin functions in vital biological processes (i.e., oxygen transport, energy production, drug metabolism), heme can be toxic at high levels. Tumor cells exploit heme to modulate their energetic metabolism, to interact with the microenvironment, and to sustain proliferation and survival [ 49 ]. In addition, modern cooking methods had been suggested to generate mutagens like heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) in meat that could mediate its carcinogenic properties [ 50 ].…”

Heme-Sensing Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics

“…Indeed, inhibition of heme synthesis has even been reported to reduce tumor cell survival and proliferation in a variety of cancer types (30,49,50). The effects of inhibiting heme synthesis may be in part due to disruption of normal cellular processes including electron transport chain function, cataplerosis in the TCA cycle, p53 activity and stability, regulating trafficking of ADP and ATP, and in circadian rhythms (48). However, our novel findings have revealed mechanistically how activation of the cellular heme-sensing pathway can regulate apoptotic priming in leukemia.…”

The battle for iron in enteric infections

“…185,186 This may also limit the adverse effects of iron supplementation on the gut. Finally, chronically high dietary iron and haem, often associated with diets rich in red meat, have been proposed to predispose towards inflammatory bowel disease and colorectal cancer, 187 both via direct effects on the epithelium and promoting dysbiosis. 188,189 Conversely, iron-deficient diets in experimental systems seem to favour the growth of protective microorganisms.…”