Selenium in the Prevention and Treatment of Hepatocellular Carcinoma: From Biomedical Investigation to Clinical Application

Abstract

Selenium is a micronutrient that had been suggested to reduce the risk of cancer. Hepatocellular carcinoma (HCC), a prevalent disease and one of the most lethal cancers in the world, awaits new alternative treatment strategies to improve patients' survival. As an essential trace element, selenium has been studied for its anticancer properties in both oxidative stress and inflammatory-related mechanisms that may contribute to HCC growth and metastasis. In recent decades, increasing studies have investigated the potential role of selenium in liver cancer involving several major cancer-associated signaling pathways, metabolic pathways, and antioxidant defense systems both in vitro and in preclinical models. It was also observed that there was an increase in the trend of development of novel selenium nanoparticles and selenium-containing inhibitors aiming to improve the therapeutic efficacy and relative potency of selenium. However, controversies remain with whether a relationship exists between serum selenium level and HCC risk. This chapter aims to summarize the multi-target and multi-pathway in vitro and in vivo pharmacological effects of selenium in HCC, to provide a more comprehensive view and to highlight the recently discovered molecular mechanisms We hope this chapter could outline the correlation of selenium level and the risk of HCC in patients and discuss the clinical application of selenium in HCC prevention and treatment.

Changes in Glutathione Content in Liver Diseases: An Update

“…Other contrasting data were reported on selenium dependent GPx. Se deficiency increases cancer incidence [311]. Hence, low Se levels have been observed in HCC patients' blood, while its supplementation decreased the risk of cancer [311].…”

“…Se deficiency increases cancer incidence [311]. Hence, low Se levels have been observed in HCC patients' blood, while its supplementation decreased the risk of cancer [311]. However, the seleno-protein GPx2 plays an important role in the progression of malignant tumors [312].…”

Antioxidant Properties of a Nanostructured Clathrate Complex Selenopyran with β-Cyclodextrin in Model Systems of Oxidative Stress

“…The use of Selenaza drug in the postoperative period promoted earlier recovery of the detoxification and synthetic function of the liver in patients with liver tumors [1]. The protective effect of selenium-containing drugs in liver diseases is determined by transformation of toxins into inactive forms in its environment, preservation of the hepatocyte membranes structure as a result of stimulation of glutathione peroxidases reducing the level of free radicals and LPO, acceleration of ethanol catabolism, and the effect on both humoral and cellular immunity [10]. Selenium is also essential for the synthesis of liver enzymes [11].…”

Diminished CCl 4 ‐induced hepatocellular carcinoma, oxidative stress, and apoptosis by co‐administration of curcumin or selenium in mice

“…This study proved the protective effect of curcumin and selenium, alone and in combination with each other, this finding in agreement with previous studies where curcumin showed multiple pharmacological activities, including anti‐inflammation and antioxidant (Xie et al, 2020), and have an essential role in inhibiting the progression of HCC through various pathways (Tan & Norhaizan, 2019; Zhang et al., 2018). Previous studies have shown a potential inverse relationship between selenium levels and the occurrence of HCC (Cheng et al., 2019).…”