Editing Apoptosis (section)

===Inhibition===
Inhibition of apoptosis can result in a number of cancers, inflammatory diseases, and viral infections. It was originally believed that the associated accumulation of cells was due to an increase in cellular proliferation, but it is now known that it is also due to a decrease in cell death. The most common of these diseases is cancer, the disease of excessive cellular proliferation, which is often characterized by an overexpression of [[inhibitor of apoptosis|IAP]] family members. As a result, the malignant cells experience an abnormal response to apoptosis induction: Cycle-regulating genes (such as p53, ras or c-myc) are mutated or inactivated in diseased cells, and further genes (such as bcl-2) also modify their expression in tumors. Some apoptotic factors are vital during mitochondrial respiration e.g. cytochrome C.<ref name="iopscience.iop.org">{{cite journal | vauthors = Kaczanowski S | title = Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging | journal = Physical Biology | volume = 13 | issue = 3 | pages = 031001 | date = May 2016 | pmid = 27172135 | doi = 10.1088/1478-3975/13/3/031001 | url = http://eprints.ibb.waw.pl/1615/1/Apoptosis2016.pdf | access-date = 2019-12-26 | url-status = dead | bibcode = 2016PhBio..13c1001K | s2cid = 5549982 | archive-url = https://web.archive.org/web/20190428231913/http://eprints.ibb.waw.pl/1615/1/Apoptosis2016.pdf | archive-date = 2019-04-28 }}</ref> Pathological inactivation of apoptosis in cancer cells is correlated with frequent respiratory metabolic shifts toward glycolysis (an observation known as the "Warburg hypothesis".<ref name="Warburg_1956">{{cite journal | vauthors = Warburg O | title = On the origin of cancer cells | journal = Science | volume = 123 | issue = 3191 | pages = 309–314 | date = February 1956 | pmid = 13298683 | doi = 10.1126/science.123.3191.309 | bibcode = 1956Sci...123..309W }}</ref>

====HeLa cell====
Apoptosis in [[HeLa]]{{efn|HeLa cells are an immortalized cancer cell line used frequently in research. The cell line was established by removing cells directly from [[Henrietta Lacks]], a cancer patient.}} cells is inhibited by proteins produced by the cell; these inhibitory proteins target retinoblastoma tumor-suppressing proteins.<ref name=DelPuerto/> These tumor-suppressing proteins regulate the cell cycle, but are rendered inactive when bound to an inhibitory protein.<ref name=DelPuerto/> HPV E6 and E7 are inhibitory proteins expressed by the human papillomavirus, HPV being responsible for the formation of the cervical tumor from which HeLa cells are derived.<ref name=Liu>{{cite journal | vauthors = Liu HC, Chen GG, Vlantis AC, Tse GM, Chan AT, van Hasselt CA | title = Inhibition of apoptosis in human laryngeal cancer cells by E6 and E7 oncoproteins of human papillomavirus 16 | journal = Journal of Cellular Biochemistry | volume = 103 | issue = 4 | pages = 1125–1143 | date = March 2008 | pmid = 17668439 | doi = 10.1002/jcb.21490 | s2cid = 1651475 }}</ref> HPV E6 causes p53, which regulates the cell cycle, to become inactive.<ref name=Niu>{{cite journal | vauthors = Niu XY, Peng ZL, Duan WQ, Wang H, Wang P | title = Inhibition of HPV 16 E6 oncogene expression by RNA interference in vitro and in vivo | journal = International Journal of Gynecological Cancer | volume = 16 | issue = 2 | pages = 743–751 | year = 2006 | pmid = 16681755 | doi = 10.1111/j.1525-1438.2006.00384.x | doi-broken-date = 27 March 2025 }}</ref> HPV E7 binds to retinoblastoma tumor suppressing proteins and limits its ability to control cell division.<ref name=Niu/>  These two inhibitory proteins are partially responsible for HeLa cells' immortality by inhibiting apoptosis to occur.<ref name="Liu McKalip">{{cite journal | vauthors = Liu Y, McKalip A, Herman B | title = Human papillomavirus type 16 E6 and HPV-16 E6/E7 sensitize human keratinocytes to apoptosis induced by chemotherapeutic agents: roles of p53 and caspase activation | journal = Journal of Cellular Biochemistry | volume = 78 | issue = 2 | pages = 334–349 | date = May 2000 | pmid = 10842327 | doi = 10.1002/(sici)1097-4644(20000801)78:2<334::aid-jcb15>3.3.co;2-6 }}</ref>

====Treatments====
{{Further|topic=a clinical pathology test that measures apoptosis|MiCK assay}}
The main method of treatment for potential death from signaling-related diseases involves either increasing or decreasing the susceptibility of apoptosis in diseased cells, depending on whether the disease is caused by either the inhibition of or excess apoptosis. For instance, treatments aim to restore apoptosis to treat diseases with deficient cell death and to increase the apoptotic threshold to treat diseases involved with excessive cell death. To stimulate apoptosis, one can increase the number of death receptor ligands (such as TNF or TRAIL), antagonize the anti-apoptotic Bcl-2 pathway, or introduce Smac mimetics to inhibit the inhibitor (IAPs).<ref name="pmid31380246">{{cite journal | vauthors = Jan R, Chaudhry GE | title = Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics | journal = Advanced Pharmaceutical Bulletin | volume = 9 | issue = 2 | pages = 205–218 | date = June 2019 | pmid = 31380246 | pmc = 6664112 | doi = 10.15171/apb.2019.024 }}</ref> The addition of agents such as Herceptin, Iressa, or Gleevec works to stop cells from cycling and causes apoptosis activation by blocking growth and survival signaling further upstream. Finally, adding p53-[[MDM2]] complexes displaces p53 and activates the p53 pathway, leading to cell cycle arrest and apoptosis. Many different methods can be used either to stimulate or to inhibit apoptosis in various places along the death signaling pathway.<ref>{{cite journal | vauthors = Boehm I | title = Apoptosis in physiological and pathological skin: implications for therapy | journal = Current Molecular Medicine | volume = 6 | issue = 4 | pages = 375–394 | date = June 2006 | pmid = 16900661 | doi = 10.2174/156652406777435390 }}</ref>

Apoptosis is a multi-step, multi-pathway cell-death programme that is inherent in every cell of the body. In cancer, the apoptosis cell-division ratio is altered. Cancer treatment by chemotherapy and irradiation kills target cells primarily by inducing apoptosis.<ref>{{cite journal |last1=Lowe |first1=Scott W. |last2=Lin |first2=Albert W. |title=Apoptosis in cancer |journal=Carcinogenesis |date=2000-03-01 |volume=21 |issue=3 |pages=485–495 |doi=10.1093/carcin/21.3.485 |pmid=10688869 |url=https://www.nature.com/articles/4401986 |access-date=2025-01-22}}</ref>