Resveratrol-Supported Bioenergetics Leads to Higher Productivity and Accompanying Endoplasmic Reticulum Stress in a...

Increasingly unpredictable market demands and the growing market of biosimilars all facilitate lower manufacturing costs. Cell culture media additives have significant potential to improve cell-specific productivity. It has been reported that the treatment of CHO cells with resveratrol results in a reduction in viable cell density and a significant increase in cell-specific productivity. In the present study, we apply our knowledge of resveratrol gained on immortal cell lines to elucidate the details of resveratrol's effects on mAb-producing CHO cells. In the present study, we confirm that resveratrol causes cell cycle arrest, which results in the increased protein productivity of mAb-producing cells. We demonstrate for the first time that resveratrol induces ER stress in mAb-producing CHO lines, presumably by increasing the amount of specific protein produced. It was found that ER stress did not induce oxidative stress, and cell viability could not be enhanced by apoptosis, necroptosis, or ferroptosis inhibitors. Therefore, these cell deaths may not play a role in the process. We also describe, for the first time, that resveratrol is able to increase ATP levels in mAb-producing CHO cells, thereby providing additional energy to mAb-producing CHO cells. This increased ATP synthesis is likely due to the intensification of respiration, not an increase in the number of mitochondria.