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Bioinformatics Database on
"Radiosensitisers and Radioprotectors"

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Methotrexate

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BIOLOGICAL TARGET

Action of Extract: Action on cell cycle:
MDA-MB-231 human breast cancer Cells exposed to low-dose methotrexate accumulated in the G1/S phase of the cell cycle.[1]
Target: Nucleic Acid
methotrexate disrupts DNA synthesis.[2]
proteins:
The combination of radiation and methotrexate enhanced the inhibition of RAD51 expression in in HOS osteosarcoma cells.[3]
Combined treatment of radiation and methotrexate induced caspase activation. and inhibited IkBα degradation in Nasal NK/T-cell lymphoma cells lines(Hank-1 and NK-92).[4]
Lipids:
sugars:
Mechanism: Intracellular purine nucleotide pool depletion by methotrexate can indirectly affect the repair of DNA damage in cells exposed to Auger electron radiation.[1]
Methotrexate is suggested to affect cell oxygenation or alter the intracellular levels of endogenous radioprotectors such as glutathione or other non-protein thiols.[5]
Combined treatment of Methotrexate and radiation significantly induced apoptosis and growth inhibition in both Nasal NK/T-cell lymphoma cells lines(Hank-1 and NK-92). The synergistic cytotoxicity was correlated with blocking radiation-induced nuclear NF-kB and suppressing expression of NF-kB-mediated anti-apoptotic proteins. [4]
REFERENCES
1. Costantini DL et al, Methotrexate, Paclitaxel, and Doxorubicin radiosensitize HER2-Amplified human breast cancer cells to the Auger electron–emitting radiotherapeutic agent 111In-NLS-Trastuzumab. J Nucl Med 2010; 51:477–483.
http://dx.doi.org/10.2967/jnumed.109.069716
2. Spittle MF, Methotrexate and radiation. Int J Radiat Oncol Biol Phys. 1978 ;4(1-2):103-7.
http://dx.doi.org/10.1016/0360-3016(78)90123-2
3. Du L et al, Correlation of RAD51 and radiosensitization of methotrexate. Chinese Journal of Radiological Medicine and Protection 2012;32(1): 44-46.
https://inis.iaea.org/search/search.aspx?orig_q=RN:46111314
4. Kim A et al, A combination of methotrexate and irradiation promotes cell death in NK/T-cell lymphoma cells via down-regulation of NF-kB signaling. Leukemia Research 2012;36:350-357.
http://dx.doi.org/10.1016/j.leukres.2011.07.027
5. Geyer JR et al, Radiation, methotrexate, and white matter necrosis: laboratory evidence for neural radioprotection with preirradiation methotrexate.Int J Radiat Oncol Biol Phys. 1988 ;15(2):373-5.
http://dx.doi.org/10.1016/S0360-3016(98)90018-9