నైరూప్య

Starvation contributes to elevated levels of heat shock proteins and cancer stem cell markers in an esophageal cancer cell line.

Amer Talib Tawfeeq, Noah Abd-Alkader Mahmood, Zaynab Saad Abd-Alghni

The presence of cancer stem cells as a subpopulation residing in the apex of solid tumor cell hierarchy has been introduced as a new hypothesis capable of describing the ability of tumors to be more aggressive, highly metastasized, and chemo-radiotherapy resistant. The origin of these cells is still controversial: one hypothesis describes the stress conditions in the tumor microenvironment as one of the driving forces behind the existence of these cells. In this study, we test if nutrition depletion conditions (deprivation of serum and glucose) would be one of such forces. Esophagus adenocarcinoma cell line SKGT-4 was exposed to starvation by depleting glucose and fetal bovine serum from growth media at different times. The viability of the cells during this condition was determined by standard MTT assay and the cells’ morphological changes were observed by crystal violet staining and trypan blue staining. The expression levels of stress-related proteins, heat shock protein 90 (HSP90) and heat shock protein 70 (HSP70), as well as some known cancer stem cell markers, CD44, ALDH1A1, and ABCG2, were determined using quantitative real-time PCR. Levels of necrosis and apoptosis were followed in cell populations under stress using a mixture of fluorescence staining and observation under a fluorescence microscope. The results indicated a loss of cell viability during the extended times of incubation in starved condition compared with the non-starved condition. Cells under starvation suffered from noticeable morphological changes combined with widespread necrosis and apoptosis. Levels of HSP90, HSP70, and cancer stem cell marker expression were significantly increased in starved condition compared with non-starved condition (p ≤ 0.01). In conclusion, although starvation as a result of serum and glucose depletion leads to induced necrosis and/or apoptosis in most of the cells, it may induce stress-resistant mechanisms in cells that remain viable (stress-resistant cells).