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177 Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is the most used radioactive agent for pain palliation in bone cancer patients. The present study aims to study the impact of relaxin-2 on the 177 Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with 177 Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. 177 Lu-EDTMP associated cellular deterioration and death was determined by LDH, MTT, and trypan blue dye assays. ELISA-based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of apoptotic-related signalling pathway proteins like bcl2, poly(ADP-ribose) polymerase (PARP), and MAPK (mitogen-activated protein kinase). Our results found that RLXH2 counters 177 Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter 177 Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in 177 Lu-EDTMP challenged cells through activation of the notch-1 pathway in a concentration- and time-dependent manner. We reported that RLXH2 significantly declined cellular toxicity and apoptosis associated with 177 Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway.

Titel:	Relaxin inhibits <superscript>177</superscript> Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway.
Autor/in / Beteiligte Person:	Xu, J ; Wan, S ; Chen, W ; Zhang, Y ; Ji, Z
Link:	Full Text Finder (Volltext)
Zeitschrift:	Acta pharmaceutica (Zagreb, Croatia), Jg. 72 (2022-10-18), Heft 4, S. 575-585
Veröffentlichung:	Warsaw, Poland : Sciendo ; <i>Original Publication</i>: Zagreb : Croatian Pharmaceutical Society, 1992-, 2022
Medientyp:	academicJournal
ISSN:	1846-9558 (electronic)
DOI:	10.2478/acph-2022-0032
Schlagwort:	Humans Apoptosis Cell Death Cell Line, Tumor Bone Neoplasms drug therapy Bone Neoplasms complications Bone Neoplasms metabolism Osteosarcoma drug therapy Osteosarcoma complications Relaxin pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Acta Pharm] 2022 Oct 18; Vol. 72 (4), pp. 575-585. <i>Date of Electronic Publication: </i>2022 Oct 18 (<i>Print Publication: </i>2022). MeSH Terms: Bone Neoplasms* / drug therapy ; Bone Neoplasms* / complications ; Bone Neoplasms* / metabolism ; Osteosarcoma* / drug therapy ; Osteosarcoma* / complications ; Relaxin* / pharmacology ; Humans ; Apoptosis ; Cell Death ; Cell Line, Tumor References: 1. M. Kansara, M. W. Teng, M. J. Smyth and D. M. Thomas, Translational biology of osteosarcoma, Nat. Rev. Cancer. 14 (11) (2014) 722–735; https://doi.org/10.1038/nrc3838. ; 2. J. M. Jimenez-Andrade, W. G. Mantyh, A. P. Bloom, A. S. Ferng, C. P. Geffre and P. W. Mantyh, Bone cancer pain, Ann. N. Y. Acad. Sci. 1198 (2010) 173–181; https://doi.org/10.1111/j.1749-6632.2009.05429.x. ; 3. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Ann. 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Contributed Indexing: Keywords: apoptosis; cell death; notch-1 pathway; osteosarcoma; relaxin-2 Substance Nomenclature: 0 (lutetium ethylenediaminetetramethylene phosphonic acid) ; 9002-69-1 (Relaxin) ; 0 (NOTCH1 protein, human) Entry Date(s): Date Created: 20230118 Date Completed: 20230123 Latest Revision: 20230403 Update Code: 20240513

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Relaxin inhibits <superscript>177</superscript> Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway.