Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.
<h4>Background</h4>To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values a...
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2013
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oai:doaj.org-article:22fd847c7d26465c843158e998cd5c9e2021-11-18T08:43:25ZResistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.1932-620310.1371/journal.pone.0082363https://doaj.org/article/22fd847c7d26465c843158e998cd5c9e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349265/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines.<h4>Results</h4>Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352%) in BLM-resistant sub-clones (p<0.05 for both). Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05). Significantly reduced DNA damage (COMET and γ-H2AX assays), G2/M arrest, and apoptosis (p<0.05 for each set of comparison) following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05).<h4>Conclusion</h4>Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.Qi WangKangping CuiOsvaldo Espin-GarciaDangxiao ChengXiaoping QiuZhuo ChenMalcolm MooreRobert G BristowWei XuSandy DerGeoffrey LiuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82363 (2013) |
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Medicine R Science Q Qi Wang Kangping Cui Osvaldo Espin-Garcia Dangxiao Cheng Xiaoping Qiu Zhuo Chen Malcolm Moore Robert G Bristow Wei Xu Sandy Der Geoffrey Liu Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| description |
<h4>Background</h4>To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines.<h4>Results</h4>Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352%) in BLM-resistant sub-clones (p<0.05 for both). Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05). Significantly reduced DNA damage (COMET and γ-H2AX assays), G2/M arrest, and apoptosis (p<0.05 for each set of comparison) following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05).<h4>Conclusion</h4>Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis. |
| format |
article |
| author |
Qi Wang Kangping Cui Osvaldo Espin-Garcia Dangxiao Cheng Xiaoping Qiu Zhuo Chen Malcolm Moore Robert G Bristow Wei Xu Sandy Der Geoffrey Liu |
| author_facet |
Qi Wang Kangping Cui Osvaldo Espin-Garcia Dangxiao Cheng Xiaoping Qiu Zhuo Chen Malcolm Moore Robert G Bristow Wei Xu Sandy Der Geoffrey Liu |
| author_sort |
Qi Wang |
| title |
Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| title_short |
Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| title_full |
Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| title_fullStr |
Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| title_full_unstemmed |
Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis. |
| title_sort |
resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced dna damage and evasion of g2/m arrest and apoptosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/22fd847c7d26465c843158e998cd5c9e |
| work_keys_str_mv |
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1718421370119913472 |