Prognostic Significance of Altered Blood and Tissue Glutathione Levels in Head and Neck Squamous Cell Carcinoma Cases

Abstract

Glutathione is a thiol compound that plays an important role in the antioxidant defense system of the cell and its deficiency leads to an increased susceptibility to oxidative stress and, thus, progression of many disease states including head and neck cancer. In the present study, alterations of glutathione levels were investigated in study cohort of 500 samples (cohort 1 containing 200 head and neck cancer blood samples along with 200 healthy controls and cohort II with 50 head and neck squamous cell carcinoma tissue samples along with 50 control tissues) by high performance liquid chromatography. The results indicated that mean blood glutathione levels were significantly reduced in head and neck cancer patients (p<0.001) compared to respective controls. In contrast, the levels of glutathione total (p<0.05) and glutathione reduced (p<0.05) were significantly elevated in head and neck squamous cell carcinoma tissues compared to the adjacent cancer-free control tissues. In addition to this, pearson correlation performed to correlate different tissue glutathione levels (GSH) with clinical/ pathological parameters demonstrated a significant negative correlation between pT-stage and GSH level (r=-0.263**; p<0.01), C-stage and GSH level (r=-0.335**; p<0.01), grade and GSH (r=-0.329**; p<0.01) and grade versus redox index (r=-0.213**; p<0.01) in HNSCC tissues. Our study suggests that dysregulation of glutathione levels in head and neck cancer has the potential to predict metastasis, and may serve as a prognostic marker.

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

“…However, alterations in GSH systems can promote tumorigenesis (Table 4). Decreased blood GSH was seen in cancer patients [233,234]. Interestingly, the GSH level was found to be increased in head and neck carcinoma [234] while the opposite was reported for colorectal cancer [235].…”

“…Decreased blood GSH was seen in cancer patients [233,234]. Interestingly, the GSH level was found to be increased in head and neck carcinoma [234] while the opposite was reported for colorectal cancer [235]. Moreover, cancer patients frequently have a decreased blood GSH and GPX activity [233,[236][237][238][239].…”

“…[241] Head and neck carcinoma Blood GSH is decreased in cancer patients, while it is increased in tumor tissue compared to adjacent normal tissue. [234] Hepatocellular carcinoma GPX4 and gamma-glutamyltransferase 1 expression is increased, while GCL, GR, GPX1, and GSS are decreased in liver tumor tissue compared to the surrounding normal tissue. [144] GSTA1 expression is downregulated in HCC and correlates with poor prognosis.…”

The Dark Chocolate against Angiogenesis?

“…Reactive oxygen species (ROS) are potential carcinogens that facilitate mutagenesis, tumor promotion and progression [38]. Food derived products exist universally and are expected to be safe, they are highly interesting for development as chemo preventive agents to treat reactive oxygen free radicals that results in cancer pathogenesis [39,40].…”