Cellular Toxicity and Apoptosis Studies in Osteocarcinoma Cells, a Comparison of 177Lu-EDTMP and Lu-EDTMP

Author(s): Chandan Kumar, Aruna Korde, Kusum V. Kumari, Tapas Das, Grace Samuel

Journal Name: Current Radiopharmaceuticals

Volume 6 , Issue 3 , 2013

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Objective: The most promising bone pain palliative agent such as 177Lu-EDTMP emerges as a newer radiopharmaceutical for cancer management. Thus, it was of interest to study the cell uptake of this agent in osteocarcinoma cell line and investigate the underlying mechanism of cellular toxicity.

Methods: The cell binding studies of 177Lu-EDTMP were carried out in osteocarcinoma cells (MG63) after induction of bone mineralization. Cellular toxicity studies were carried out with varying amounts of 177Lu-EDTMP and compared with equivalent amount of cold Lu-EDTMP. Cell viability was assessed by trypan blue, LDH and MTT assay. Different studies such as DNA fragmentation and Western blotting for apoptosis related proteins were carried out to elucidate the mechanism of cell death.

Results: Maximum cell binding of 177Lu-EDTMP, observed with mineralized MG63 cells was 19 ± 0.122 %. Nearly 12% cell death was observed in MG63 cells treated with 37 MBq of 177Lu-EDTMP as compared to controls. Apoptosis studies were carried out by ELISA to estimate DNA fragmentation and it was found that DNA enrichment factor was 1.8, compared to the corresponding control. Down regulation of anti-apoptotic protein, bcl-2 and cleavage of PARP protein was evident by Western blot results.

Conclusion: These studies indicate that the 177Lu-EDTMP binds to mineralized bone cells and induces apoptotic cell death in MG63 cells.

Keywords: Apoptosis, Cellular toxicity, Lu 177-EDTMP, Cell uptake, Bone mineralization, Osteocarcinoma.

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Article Details

Year: 2013
Page: [146 - 151]
Pages: 6
DOI: 10.2174/18744710113069990021
Price: $65

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