Cytostasis Explained

Cytostasis (cyto – cell; stasis – stoppage) is the inhibition of cell growth and multiplication. Cytostatic refers to a cellular component or medicine that inhibits cell division and induce cell death.^{[1] [2]}

Cytostasis is an important prerequisite for structured multicellular organisms. Without regulation of cell growth and division only unorganized heaps of cells would be possible.

Chemotherapy of cancer, treatment of skin diseases and treatment of infections are common use cases of cytostatic drugs; although they can also affect normal and healthy cells and tissues.^{[3] [4]} Active hygienic products generally contain cytostatic substances.

Cytostatic mechanisms and drugs generally occur together with cytotoxic ones.

Activators

Nitric oxide – activated macrophages produce large amounts of nitric oxide (NO), which induces both cytostasis and cytotoxicity to tumor cells both in vitro and in vivo. Nitric oxide-induced cytostasis targets ribonucleotide reductase by rapid and reversible inhibition. However, other studies show there could be other targets that are responsible for producing long-lasting cytostasis in cells.^[5]

Lipopolysaccharide (LPS) and lipid A-associated protein – studies have demonstrated that LPS and LAP are potent macrophage activators that have been shown to stimulate tumoricidal (cytostatic) activity in vitro. LAP and LPS were shown to stimulate C3H/HeJ macrophages to kill target tumor cells. It was concluded that LAP can deliver at least one of the triggering signals necessary for inducing macrophage activity that leads to cytostasis.^[6]

Polyunsaturated fatty acid – N-3 and n-6 polyunsaturated fatty acids were found to have a distinct effect on cell growth in certain human urothelial cells. Cystostatic concentrations of n-3 and n-6 PUFA did not induce apoptosis, but did cause permanent cellular growth arrest by effecting the cell cycle. Study shows that metabolites of the lipoxygenase pathway are involved with the antiproliferation induce by PUFA. However, PUFA cytostatic activity is not tumor-specific.^[7]

Medical uses

Cytostatic agents have been beneficial in fighting tumors with their ability to induce cell growth arrest. After administration, they are expelled from the body through urine and feces, which ultimately reach wastewater systems, posing a risk to the aquatic ecosystem.^{[8] [9] [10] [11] [12]} Although the risks have not been widely studied and more research is needed in this area.^{[13] [14] [15]}

Breast cancer – One study indicates nitric oxide (NO) is able to have a cytostatic effect on the human breast cancer cell line MDA-MB-231. Not only does nitric oxide stop cell growth, the study shows that it can also induce apoptosis after the cancer cells have been exposed to NO over 48 hours.

Malignant epithelium – Long-chain polyunsaturated fatty acids inhibit cell division, cause cell cycle arrest, and can induce cell death in malignant epithelial cells from various tissue organs in vitro.

See also

• Chemotherapy

Notes and References

1. Jureczko . Marcelina . Przystaś . Wioletta . 2024-07-10 . Toxicity toward freshwater and marine water organisms of the cytostatic drugs bleomycin and vincristine and their binary mixture . Science of the Total Environment . 933 . 173175 . 10.1016/j.scitotenv.2024.173175 . 38750736 . 2024ScTEn.93373175J . 0048-9697.
2. Gouveia . Teresa I. A. . Alves . Arminda . Santos . Mónica S. F. . 2019-12-01 . New insights on cytostatic drug risk assessment in aquatic environments based on measured concentrations in surface waters . Environment International . 133 . Pt B . 105236 . 10.1016/j.envint.2019.105236 . 31675568 . 2019EnInt.13305236G . 0160-4120. 10216/127536 . free .
3. Gouveia . Teresa I. A. . Alves . Arminda . Santos . Mónica S. F. . 2019-12-01 . New insights on cytostatic drug risk assessment in aquatic environments based on measured concentrations in surface waters . Environment International . 133 . Pt B . 105236 . 10.1016/j.envint.2019.105236 . 31675568 . 2019EnInt.13305236G . 0160-4120. 10216/127536 . free .
4. Brezovšek . Polona . Eleršek . Tina . Filipič . Metka . 2014-04-01 . Toxicities of four anti-neoplastic drugs and their binary mixtures tested on the green alga Pseudokirchneriella subcapitata and the cyanobacterium Synechococcus leopoliensis . Water Research . 52 . 168–177 . 10.1016/j.watres.2014.01.007 . 24472702 . 2014WatRe..52..168B . 0043-1354.
5. Pervin. S.. Singh, R. . Chaudhuri, G. . Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): Potential role of cyclin D1. Proceedings of the National Academy of Sciences. 13 March 2001. 98. 6. 3583–3588. 10.1073/pnas.041603998. 30696. 11248121. free. 2001PNAS...98.3583P .
6. Chapes. SK. Killion, JW . Morrison, DC . Tumor cell killing and cytostasis by C3H/HeJ macrophages activated in vitro by lipid A-associated protein and interferon gamma.. Journal of Leukocyte Biology. Mar 1988. 43. 3. 232–7. 3125294. 10.1002/jlb.43.3.232. 2481166.
7. Diggle . N-3 and n-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p52 gene function . Journal of Lipid Research . 2000 . 41 . 9 . 1509–1515 . 10.1016/S0022-2275(20)33463-5 . 10974058. etal. free .
8. Gouveia . Teresa I.A. . Alves . Arminda . Santos . Mónica S.F. . 2019-12-01 . New insights on cytostatic drug risk assessment in aquatic environments based on measured concentrations in surface waters . Environment International . 133 . Pt B . 105236 . 10.1016/j.envint.2019.105236 . 31675568 . 2019EnInt.13305236G . 0160-4120. 10216/127536 . free .
9. Jureczko . Marcelina . Przystaś . Wioletta . 2024-07-01 . Toxicity toward freshwater and marine water organisms of the cytostatic drugs bleomycin and vincristine and their binary mixture . Science of the Total Environment . 933 . 173175 . 10.1016/j.scitotenv.2024.173175 . 2024ScTEn.93373175J . 0048-9697.
10. Angelakis . Andreas N. . Valipour . Mohammad . Choo . Kwang-Ho . Ahmed . Abdelkader T. . Baba . Alper . Kumar . Rohitashw . Toor . Gurpal S. . Wang . Zhiwei . 2021-08-16 . Desalination: From Ancient to Present and Future . Water . en . 13 . 16 . 2222 . 10.3390/w13162222 . free . 2073-4441. 11147/11590 . free .
11. Santos . Mónica S.F. . Franquet-Griell . Helena . Lacorte . Silvia . Madeira . Luis M. . Alves . Arminda . 2017-10-01 . Anticancer drugs in Portuguese surface waters – Estimation of concentrations and identification of potentially priority drugs . Chemosphere . 184 . 1250–1260 . 10.1016/j.chemosphere.2017.06.102 . 28672724 . 2017Chmsp.184.1250S . 0045-6535.
12. Tauxe-Wuersch . Annick . De Alencastro . Luiz Felippe . Grandjean . Dominique . Tarradellas . Joseph . 2006-06-15 . Trace determination of tamoxifen and 5-fluorouracil in hospital and urban wastewaters . International Journal of Environmental Analytical Chemistry . en . 86 . 7 . 473–485 . 10.1080/03067310500291502 . 2006IJEAC..86..473T . 0306-7319.
13. Franquet-Griell . Helena . Gómez-Canela . Cristian . Ventura . Francesc . Lacorte . Silvia . 2017-10-01 . Anticancer drugs: Consumption trends in Spain, prediction of environmental concentrations and potential risks . Environmental Pollution . 229 . 505–515 . 10.1016/j.envpol.2017.06.011 . 28628866 . 2017EPoll.229..505F . 0269-7491.
14. Martín . Julia . Camacho-Muñoz . Dolores . Santos . Juan Luis . Aparicio . Irene . Alonso . Esteban . 2014-02-16 . Occurrence and Ecotoxicological Risk Assessment of 14 Cytostatic Drugs in Wastewater . Water, Air, & Soil Pollution . en . 225 . 3 . 1896 . 10.1007/s11270-014-1896-y . 2014WASP..225.1896M . 1573-2932.
15. Gouveia . Teresa I.A. . Alves . Arminda . Santos . Mónica S.F. . 2019-12-01 . New insights on cytostatic drug risk assessment in aquatic environments based on measured concentrations in surface waters . Environment International . 133 . Pt B . 105236 . 10.1016/j.envint.2019.105236 . 31675568 . 2019EnInt.13305236G . 0160-4120. 10216/127536 . free .