A mechanistic view of the use of cold temperature in the treatment of cancer

Abstract

In their latest article, Seki and colleagues investigate the potential role of cold as a therapeutical option to treat various cancer types, including even clinically untreatable cancers such as pancreatic cancers. The authors suggest that cold exposure may have a tumor-suppressive effect mediated by the activation of brown adipose tissue (BAT), in charge of dissipating heat through non-shivering thermogenesis. In this regard, circulating blood glucose is decreased, restricting the tumor glucose uptake, which is redistributed, favoring BAT uptake to fuel thermogenesis.¹.

Keywords: Cancer systems biology; Cell biology; Lipid.

Figure 1

Effect of cold in thermoregulation and NAD⁺ synthesis Cold exposure activates SNS, releasing norepinephrine that binds to β-adrenergic receptors inducing WAT lipolysis BAT stimulation, and UCP1 activation favoring, thus, non-shivering thermogenesis that is mediated by UCP1. UCP1 activation generates heat that is used for thermogenesis. Alongside, the apoptosis-inducing mitochondrion-associated factor 2 (Aifm2) translocates into the mitochondria, where it oxidizes NADH to maintain high cytosolic NAD⁺ levels, promoting glycolysis and the electron transport chain activity required to fuel heat generation for thermogenesis. Redistribution of glucose uptake upon cold exposure, starves tumors from their main source of fuel, while favoring UPC1 heat generation and boosting most likely NAD⁺ concentrations, a key molecule demonstrated to present antitumorigenic properties.