Vishal Sharma & Ramandeep Kaur & Archana Bhatnagar & Jagdeep Kaur

Abstract

The acidic microenvironment around tumor cells is a major determinant in cancer growth, metabolism, and metastasis. However, its role in cancer physiology is still not clearly understood. In the present investigation, an attempt has been made to explore the effect of an acidic environment on the physiology of cancer cells. Exposure of Raji cells to the extracellular acidic environment was associated with enhanced cytosolic calcium level and endoplasmic reticulum stress response. X-box binding protein 1 (XBP1) splicing, CCAAT/enhancer-binding protein homologous protein (CHOP), and
glucose-regulated protein 78 kDa (GRP78) upregulation suggested
endoplasmic reticulum stress generation. On the other hand, real-time-based upregulation of Bax gene expression and flow cytometric analysis of cytochrome c release as well as enhanced act ive caspase-3 further confirmed mitochondrion-mediated events leading to induction of apoptosis. The expression of TP53 and p21 was upregulated. These observations collectively strongly suggest that both endoplasmic reticulum stress-mediated calcium release and Bax targeting might be altering mitochondrionmembrane potential which in turn could induce secondary apoptotic signals; subsequently, endoplasmic reticulum stress can also lead to nuclear localization of Nuclear factor-κB (NF-κB) which in turn favors p53 mediated apoptotic signals.