Differential sensitivity to mitomycin C between human RSa cell line and its derivative UVr-1.
To study cellular signaling factors responsible for the susceptibility of human cells to cell proliferation inhibition by anticancer drugs, human RSa cell line and its ultraviolet-resistant derivative UVr-1 were compared with respect to their sensitivity to the anti-proliferative effects of mitomycin C (MMC), 5-fluorouracil, nimustine (ACNU), cisplatin, pirarubicin (THP), bleomycin, methotrexate and ifosfamide. RSa cells were found to be highly sensitive to MMC by MTT assay compared to UVr-1 cells. The half maximum inhibition concentration of MMC against proliferation of RSa cells was approximately 100 ng/ml while that of UVr-1 cells was greater than 1 microgram/ml. There was no significant difference observed between RSa and UVr-1 cells in the sensitivity to other seven drugs examined. Analysis by flow cytometry revealed that the cell cycle of RSa was completely blocked at the G2/M phase 40 h after treatment with MMC at a concentration of 100 ng/ml whereas a substantial proportion of UVr-1 cells was not arrested at that phase even in the presence of MMC. Further immunoblot analysis on MMC-induced signal transduction showed that the amounts of phosphorylated ERK MAP kinases were increased in UVr-1 cells to a greater extent than those in RSa cells after treatment with MMC for longer than 2 h. However, the increase in p21Cip1 was observed in RSa cells 1 h after addition of MMC but was not observed in UVr-1 cells. These distinct signaling pathways might account for the differences in sensitivity to MMC between RSa and UVr-1 cells.
Hiwasa
T
T
Department of Biochemistry, School of Medicine, Chiba University, Japan. hiwasa med.m.chiba-u.ac.jp
Chen
Z
Z
Nomura
J
J
Yamamori
H
H
Tashiro
T
T
Nakajima
N
N
Suzuki
N
N
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D002999:Clone Cells; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007069:Ifosfamide / Q000494:pharmacology; D015151:Immunoblotting; D008727:Methotrexate / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology*; D015376:Nimustine / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003432:Cross-Linking Reagents; D015376:Nimustine; D001761:Bleomycin; D016685:Mitomycin; D004317:Doxorubicin; C027260:pirarubicin; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide; D008727:Methotrexate