Int J Biol Sci 2018; 14(13):1800-1812. doi:10.7150/ijbs.26962 This issue


Evaluating the Remote Control of Programmed Cell Death, with or without a Compensatory Cell Proliferation

Xixi Dou1,2✉, Lichan Chen3✉, Mingjuan Lei4, Lucas Zellmer5, Qingwen Jia1, Peixue Ling1,2, Yan He6, Wenxiu Yang7, Dezhong Joshua Liao6,7✉

1. Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, Shandong Province, P.R. China
2. Technology Center, Shandong Freda Pharmaceutical Group, Jinan 250101, Shandong Province, P.R. China
3. College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, P.R. China
4. Hormel Institute, University of Minnesota, Austin, MN 55912, USA
5. Masonic Cancer Center, University of Minnesota, 435 E. River Road, Minneapolis, MN 55455, USA
6. Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China in Guizhou Medical University, Guiyang 550004, Guizhou Province, P.R. China
7. Department of Pathology, Guizhou Medical University Hospital, Guiyang 550004, Guizhou province, P.R. China

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Dou X, Chen L, Lei M, Zellmer L, Jia Q, Ling P, He Y, Yang W, Liao DJ. Evaluating the Remote Control of Programmed Cell Death, with or without a Compensatory Cell Proliferation. Int J Biol Sci 2018; 14(13):1800-1812. doi:10.7150/ijbs.26962. Available from

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Graphic abstract

Organisms and their different component levels, whether organelle, cellular or other, come by birth and go by death, and the deaths are often balanced by new births. Evolution on the one hand has built demise program(s) in cells of organisms but on the other hand has established external controls on the program(s). For instance, evolution has established death program(s) in animal cells so that the cells can, when it is needed, commit apoptosis or senescent death (SD) in physiological situations and stress-induced cell death (SICD) in pathological situations. However, these programmed cell deaths are not predominantly regulated by the cells that do the dying but, instead, are controlled externally and remotely by the cells' superior(s), i.e. their host tissue or organ or even the animal's body. Currently, it is still unclear whether a cell has only one death program or has several programs respectively controlling SD, apoptosis and SICD. In animals, apoptosis exterminates, in a physiological manner, healthy but no-longer needed cells to avoid cell redundancy, whereas suicidal SD and SICD, like homicidal necrosis, terminate ill but useful cells, which may be followed by regeneration of the live cells and by scar formation to heal the damaged organ or tissue. Therefore, “who dies” clearly differentiates apoptosis from SD, SICD and necrosis. In animals, apoptosis can occur only in those cell types that retain a lifelong ability of proliferation and never occurs in those cell types that can no longer replicate in adulthood. In cancer cells, SICD is strengthened, apoptosis is dramatically weakened while SD has been lost. Most published studies professed to be about apoptosis are actually about SICD, which has four basic and well-articulated pathways involving caspases or involving pathological alterations in the mitochondria, endoplasmic reticula, or lysosomes.

Keywords: Apoptosis, Stress-induced cell death, Senescent death, Necrosis, Cancer, Evolution, Regeneration