Nutrient deprivation induces autophagy as well as apoptosis in Chinese hamster ovary cell culture

Abstract

During Chinese hamster ovary (CHO) cell culture for foreign protein production, cells are subjected to programmed cell death (PCD). A rapid death at the end of batch culture is accelerated by nutrient starvation. In this study, type 11 PCD, autophagy, as well as type I PCD, apoptosis, was found to take place in two antibody-producing CHO cell lines, Ab1 and Ab2, toward the end of batch culture when glucose and glutamine were limiting. The evidence of autophagy was observed from the accumulation of a common autophagic marker, a 16 kDa form of LC3-II during batch culture. Moreover, a significant percentage of the total cells (80% of Ab1 cells and 86% of Ab2 cells) showed autophagic vacuoles containing cytoplasmic material by transmission electron microscopy. An increased level of PARP cleavage and chromosomal DNA fragmentation supported that starvation-induced apoptosis also occurred simultaneously with autophagy.