Jee Young Kim1, Xinlai Cheng2, Stefan Wölfl3. 1. Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: j.kim@uni-heidelberg.de. 2. Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: x.cheng@uni-heidelberg.de. 3. Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: wolfl@uni-hd.de.
Abstract
BACKGROUND: Low extracellular pH (pHe) is a common hallmark of tumor microenvironment, which will also affect pH sensitive T-lymphocytes in this environment. Due to the growing interest on T-cell mediated cancer therapies, acidic stress induced consequences on this lymphocyte deserves through investigations. RESULTS: In line with our previous study [Kim et al., Biochem. Biophys. Res. Commun. 2016; 472(4): 585-91.], we applied sub-lethal acidic stress (pH 3.3, 37°C for 25min) to Jurkat T-lymphocytes. Progression from early apoptosis into late apoptosis was clearly observed by flow cytometry within 3 days. Treatment led to onset of G1 arrest in the first 24h and cell cycling data corresponded to survival of an invasive alkaline phosphatase (AP) positive population. Concerning the massive cell death observed after 72h, both mRNA level (qRT-PCR) and protein level (western blotting) data indicate programmed cell death through p53-p21 independent signaling. CONCLUSION: Taken together, the results obtained suggest that the majority of Jurkat cells exposed to short but intense acidic stress conditions, as used here, undergo intrinsic apoptosis, while invasion and AP activation only occurred in a small surviving cell population.
BACKGROUND: Low extracellular pH (pHe) is a common hallmark of tumor microenvironment, which will also affect pH sensitive T-lymphocytes in this environment. Due to the growing interest on T-cell mediated cancer therapies, acidic stress induced consequences on this lymphocyte deserves through investigations. RESULTS: In line with our previous study [Kim et al., Biochem. Biophys. Res. Commun. 2016; 472(4): 585-91.], we applied sub-lethal acidic stress (pH 3.3, 37°C for 25min) to Jurkat T-lymphocytes. Progression from early apoptosis into late apoptosis was clearly observed by flow cytometry within 3 days. Treatment led to onset of G1 arrest in the first 24h and cell cycling data corresponded to survival of an invasive alkaline phosphatase (AP) positive population. Concerning the massive cell death observed after 72h, both mRNA level (qRT-PCR) and protein level (western blotting) data indicate programmed cell death through p53-p21 independent signaling. CONCLUSION: Taken together, the results obtained suggest that the majority of Jurkat cells exposed to short but intense acidic stress conditions, as used here, undergo intrinsic apoptosis, while invasion and AP activation only occurred in a small surviving cell population.
Authors: Jee Young Kim; Thien T P Dao; Kwangho Song; Sait Byul Park; Hyeri Jang; Min Kyoung Park; Soo Ueng Gan; Yeong Shik Kim Journal: Evid Based Complement Alternat Med Date: 2018-07-17 Impact factor: 2.629