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01-08-2012 | PRECLINICAL STUDIES

Salinomycin, a p-glycoprotein inhibitor, sensitizes radiation-treated cancer cells by increasing DNA damage and inducing G2 arrest

Authors: Won Ki Kim, Ju-Hwa Kim, Kyungsil Yoon, Sunshin Kim, Jungsil Ro, Han Sung Kang, Sungpil Yoon

Published in: Investigational New Drugs | Issue 4/2012

Summary

Salinomycin (Sal) is potentially useful for the treatment of cancer. The present study examined a novel mechanism of Sal sensitization in cancer cells. Sal sensitized radiation-treated cancer cells by inducing G2 arrest and causing DNA damage. Sal treatment also reduced p21 levels in radiation-treated cells. Considering that Sal sensitizes doxorubicin (DOX)- or etoposide (ETO)-treated cancer cells by causing DNA damage and reducing p21 expression, the results from our study suggest that the mechanism underlying Sal sensitization is conserved in both chemo- and radiation-treated cells. We also tested the ability of Sal to inhibit p-glycoprotein (P-gp), which plays a role in the efflux of anti-cancer drugs to reduce cellular damage. In particular, we compared Sal to verapamil (Ver), a well-known P-gp inhibitor. Sal inhibits P-gp with a different substrate distinct from that of Ver. In addition, Sal sensitized Ver-resistant cells, indicating that this compound is more effective for sensitizing than Ver. Taken together, the results from our study may contribute to the development of Sal-based therapy for cancer patients treated with P-gp-inhibiting drugs or radiation therapy.

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Title: Salinomycin, a p-glycoprotein inhibitor, sensitizes radiation-treated cancer cells by increasing DNA damage and inducing G2 arrest
Authors: Won Ki Kim
Ju-Hwa Kim
Kyungsil Yoon
Sunshin Kim
Jungsil Ro
Han Sung Kang
Sungpil Yoon
Publication date: 01-08-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-011-9685-6

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