Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer

Abstract

Obesity is a significant risk factor for various cancers including breast cancer resulting in an increased risk of recurrence as well as morbidity and mortality. Extensive studies on various pathways have been successful in establishing a biological relationship between obesity and breast cancer. The molecular classification of breast cancer includes five groups each having different responses to treatment. Increased levels of inflammatory cytokines seen in obese conditions drive the pro-proliferative pathways, such as the influx of macrophages, angiogenesis, and antiapoptotic pathways. Increased peripheral aromatization of androgens by aromatase increases the circulating estrogen levels which are also responsible for the association of obesity with breast cancer. Also, increased oxidative stress due to chronic low-grade inflammation in obese women plays an important role in carcinogenesis. Despite the availability of safe and effective treatment options for breast cancer, obese women are at increased risk of adverse outcomes including treatment-related toxicities. In the recent decade, selenium compounds have gained substantial interest as chemopreventive and anticancer agents. The chemical derivatives of selenium include inorganic and organic compounds that exhibit pro-oxidant properties and alter cellular redox homeostasis. They target more than one metabolic pathway by thiol modifications, induction of reactive oxygen species, and chromatin modifications to exert their chemopreventive and anticancer activities. The primary functional effectors of selenium that play a significant role in human homeostasis are selenoproteins like glutathione peroxidase, thioredoxin reductase, iodothyronine deiodinases, and selenoprotein P. Selenoproteins play a significant role in adipose tissue physiology by modulating preadipocyte proliferation and adipogenic differentiation. They correlate negatively with body mass index resulting in increased oxidative stress that may lead to carcinogenesis in obese individuals. Methylseleninic acid effectively suppresses aromatase activation thus reducing the estrogen levels and acting as a breast cancer chemopreventive agent. Adipose-derived inflammatory mediators influence the selenium metabolites and affect the proliferation and metastatic properties of cancer cells. Recently selenium nanoparticles have shown potent anticancer activity which may lead to a major breakthrough in the management of cancers caused due to multiple pathways. In this review, we discuss the possible role of selenoproteins as chemopreventive and an anticancer agent in obese breast cancer.

Metformin and tBHQ Treatment Combined with an Exercise Regime Prevents Osteosarcopenic Obesity in Middle‐Aged Wistar Female Rats

“…This is consistent with some reports in which it has been determined that obesity is a significant risk factor for various cancers, including breast cancer, resulting in an increased risk, as well as morbidity and mortality. Higher inflammatory cytokine levels during obesity induce the proliferative pathways, such as macrophages infiltration, angiogenesis, and antiapoptotic pathways [ 50 , 51 ]. Adipose tissue generates a chronic low-grade inflammatory state which also contributes to increased oxidative stress [ 8 , 12 ]; it is known that both exercise and MTF reduce adipose tissue and consequently decrease inflammatory state and oxidative stress, and the latter have linked it to an increase in life expectancy [ 13 , 14 , 41 ].…”

The Role of Selenium in Pathologies: An Updated Review

“…A very recent meta-analysis on 18 case-control studies investigated the relationship between selenium levels in human tissue and breast cancer risk, highlighting a negative correlation [ 90 ]. In this context, a similar study [ 91 ] focusing on breast cancer in obese patients, showed that decreased levels of selenoproteins in the adipose tissue of obese subjects resulted in an inflammatory state that may progress to cancer.…”

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

“…The second pathway that was targeted by 93% of the top drugs was the biological oxidation pathway. Increased oxidative stress plays a role in carcinogenesis in breast cancer patients [ 115 ]. In a study of the immune microenvironment of breast cancer, oxidative stress in combination with other biological phenotypes was associated with high immune infiltration [ 116 ].…”