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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/02 16:32:04」(JST)

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Cytostasis(cyto - cell, stasis - stoppage) is the inhibition of cell growth and multiplication. Cytostatic refers to a cellular component or medicine that inhibits cell growth.

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. Active hygienic products generally contain cytostatic substances.

Cytostatic mechanisms and drugs generally occur together with cytotoxic ones.

Cytostasis 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.^[1]

Lipopolysaccharide 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.^[2]

Polyunsaturated fatty acid - N-3 and n-6 polyunsaturated fatty acids were found to have a distinct affect 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^[3]

Medical Uses of Cytostasis

Cytostatic Agents have been beneficial in fighting tumors with their ability to induce cell growth arrest. Breast Cancer - one study indicates on nitric oxide 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^[1]

Malignant Epithelium - Long-chain polyunsaturated fatty acids inhibit cell division, cause cell cycle arrest, and can even induce cell death in malignant epithelial cells from various tissue organs in vitro^[3]

References

^ ^a ^b Pervin, S.; Singh, R.; Chaudhuri, G. (13 March 2001). "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 98 (6): 3583–3588. doi:10.1073/pnas.041603998. PMC 30696. Cite uses deprecated parameters (help)
^ Chapes, SK; Killion, JW; Morrison, DC (Mar 1988). "Tumor cell killing and cytostasis by C3H/HeJ macrophages activated in vitro by lipid A-associated protein and interferon gamma.". Journal of leukocyte biology 43 (3): 232–7. PMID 3125294. Cite uses deprecated parameters (help)
^ ^a ^b Diggle, et al. "N-3 and n-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p52 gene function." Journal of Lipid Research. Vol 41, 2000

English Journal

Metabolism of doxorubicin to the cardiotoxic metabolite doxorubicinol is increased in a mouse model of chronic glutathione deficiency: A potential role for carbonyl reductase 3.

Schaupp CM1, White CC1, Merrill GF2, Kavanagh TJ3.
Chemico-biological interactions.Chem Biol Interact.2015 Jun 5;234:154-61. doi: 10.1016/j.cbi.2014.11.010. Epub 2014 Nov 21.
Doxorubicin is highly effective at inducing DNA double-strand breaks in rapidly dividing cells, which has led to it being a widely used cancer chemotherapeutic. However, clinical administration of doxorubicin is limited by off-target cardiotoxicity, which is thought to be mediated by doxorubicinol,
PMID 25446851

Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple-Negative Breast Cancer.

Parvani JG1, Gujrati MD2, Mack MA2, Schiemann WP3, Lu ZR4.
Cancer research.Cancer Res.2015 Jun 1;75(11):2316-25. doi: 10.1158/0008-5472.CAN-14-3485. Epub 2015 Apr 9.
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and dr
PMID 25858145

Maid is a negative regulator of transforming growth factor-β-induced cell migration.

Motizuki M1, Saitoh M1, Miyazawa K2.
Journal of biochemistry.J Biochem.2015 May 22. pii: mvv054. [Epub ahead of print]
Maternal Id-like molecule (Maid) is a dominant negative helix-loop-helix protein that has been implicated in regulating gene expression as well as cell-cycle progression. Overexpressed Maid was previously shown to inhibit certain cellular responses induced by transforming growth factor-β (TGF-β),
PMID 26002959

Japanese Journal

レクチンの細胞増殖抑制効果ならびに細胞内挙動の追跡

水野貴伯,松井弘斗,草間健 [他]
杉山産業化学研究所年報 2009年, 1-12, 2009-00-00
NAID 40017223528

Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis

HOSTEIN I.
Cancer Res 61, 4003-4009, 2001
NAID 80012519445

77(P-71) Securidaca inappendiculataより単離されたマクロファージ細胞死誘導活性物質の構造(ポスター発表の部)

黒田明平,三巻祥浩,指田豊,油井聡,山崎正利,北原幹郎
天然有機化合物討論会講演要旨集 (42), 457-462, 2000-10-01
… By bioassay-guided fractionation of the n-BuOH-soluble phase, two new acylated triterpene saponins (1, 2) were isolated as the active constituents responsible for the macrophages cytostasis. …
NAID 110006681979