Glucocorticoids and Cancer

Abstract

Unlike other steroid hormone receptors, the glucocorticoid receptor (GR) is not considered an oncogene. In breast cancer, the estrogen receptor (ER) drives cell growth, proliferation, and metastasis, and the androgen receptor (AR) plays a similar role in prostate cancer. Accordingly, treatment of these diseases has focused on blocking steroid hormone receptor function. In contrast, glucocorticoids (GCs) work through GR to arrest growth and induce apoptosis in lymphoid tissue. Glucocorticoids are amazingly effective in this role, and have been deployed as the cornerstone of lymphoid cancer treatment for decades. Unfortunately, not all patients respond to GCs and dosage is restricted by immediate and long term side effects. In this chapter we review the treatment protocols that employ glucocorticoids as a curative agent, elaborate on what is known about their mechanism of action in these cancers, and also summarize the palliative uses of glucocorticoids for other cancers.

The triterpene echinocystic acid and its 3-O-glucoside derivative are revealed as potent and selective glucocorticoid receptor agonists

“…In addition to their anti-inflammatory actions, GCs are well known for their cell type specific effect on induction of apoptosis (Gruver-Yates and Cidlowski, 2013) that give rise to their use as anticancer agents, in the treatment of specific type of cancers (Pufall, 2015). The molecular mechanisms of the GCs-mediated induction of apoptosis involve down regulation or inhibition of anti-apoptotic molecules, such as Bcl-2, as well as upregulation or activation of pro-apoptotic molecules such as BAX-2 (Lotem and Sachs, 1995;Salomons et al, 1997;Rieger et al, 1999;Murphy et al, 2000;Das et al, 2004;Almawi et al, 2004;Hoijman et al, 2004;Mahmoud et al, 2009;Lopez-Royuela et al, 2010;Melarangi et al, 2012;Zaman et al, 2014).…”

In Vitro Toxicity of Asparagus Saponins in Distinct Multidrug‐Resistant Colon Cancer Cells

“…These compounds are steroid hormones that are either secreted from the adrenal gland during exposure to acute and chronic stressors or administered pharmacologically to reduce inflammation and currently they are been used as new therapy mainly from solid tumors. [9] Plant steroids share structural similarities with glucocorticoids ( Figure 1).…”

Intrathecal betamethasone for cancer pain: A study of its analgesic efficacy and safety

“…The immediate effects caused by glucocorticoids are thought to be mediated via a non‐genomic mechanism of action, such as an effect on specific membrane‐bound receptors or intracellular signal transmission, rather than a nuclear mechanism of action . Glucocorticoids have also been shown to induce apoptosis of cancer cells via activation of caspase in the mitochondrial pathway, and the development of cancer immunotherapies related to glucocorticoids and their receptors is progressing …”