Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway
177Lu-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 177Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were...
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2022-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2022-0032 |
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| author | Xu Junhua Wan Song Chen Wei Zhang Yi Ji Zhenzhong |
| author_facet | Xu Junhua Wan Song Chen Wei Zhang Yi Ji Zhenzhong |
| author_sort | Xu Junhua |
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| description | 177Lu-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 177Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with 177Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. 177Lu-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 177Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter 177Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in 177Lu-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 177Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway. |
| format | Article |
| id | doaj-art-60c73b14846249178a88c8151c348601 |
| institution | Kabale University |
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| language | English |
| publishDate | 2022-12-01 |
| publisher | Sciendo |
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| series | Acta Pharmaceutica |
| spelling | doaj-art-60c73b14846249178a88c8151c3486012025-02-02T23:44:34ZengSciendoActa Pharmaceutica1846-95582022-12-0172457558510.2478/acph-2022-0032Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathwayXu Junhua0Wan Song1Chen Wei2Zhang Yi3Ji Zhenzhong4Department of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080ChinaDepartment of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080ChinaDepartment of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080ChinaDepartment of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080ChinaDepartment of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080China177Lu-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 177Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with 177Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. 177Lu-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 177Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter 177Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in 177Lu-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 177Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway.https://doi.org/10.2478/acph-2022-0032osteosarcomarelaxin-2cell deathapoptosisnotch-1 pathway |
| spellingShingle | Xu Junhua Wan Song Chen Wei Zhang Yi Ji Zhenzhong Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway Acta Pharmaceutica osteosarcoma relaxin-2 cell death apoptosis notch-1 pathway |
| title | Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway |
| title_full | Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway |
| title_fullStr | Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway |
| title_full_unstemmed | Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway |
| title_short | Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway |
| title_sort | relaxin inhibits 177lu edtmp associated cell death in osteosarcoma cells through notch 1 pathway |
| topic | osteosarcoma relaxin-2 cell death apoptosis notch-1 pathway |
| url | https://doi.org/10.2478/acph-2022-0032 |
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