Abstract:
:V-ATPases are proton-translocating enzymes, which are found not only in numerous intracellular organelles but also in the plasma membranes of many eukaryotic cells. Using differential display, we have identified one of the proton pump subunit genes, ATP6C, as a cisplatin-inducible gene. Northern blot analysis demonstrated that expression of other members of the subunit is inducible by cisplatin treatment. Proton pump gene expression is also upregulated in 3 independent cisplatin-resistant cell lines but not in vincristine- or etoposide-resistant cell lines. Cellular pH was significantly higher in cisplatin-resistant cells than in sensitive parental cells. In vitro DNA-binding activity of cisplatin was markedly increased in acidic conditions, suggesting that the cytotoxicity of cisplatin is modulated by cellular pH. Furthermore, the proton pump inhibitor bafilomycin can synergistically potentiate the cytotoxicity of cisplatin but not of etoposide or camptothecin. These results indicate that cellular pH is one of the critical parameters for effective cancer chemotherapy with cisplatin.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Murakami T,Shibuya I,Ise T,Chen ZS,Akiyama S,Nakagawa M,Izumi H,Nakamura T,Matsuo K,Yamada Y,Kohno Kdoi
10.1002/ijc.1418keywords:
subject
Has Abstractpub_date
2001-09-01 00:00:00pages
869-74issue
6eissn
0020-7136issn
1097-0215pii
10.1002/ijc.1418journal_volume
93pub_type
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