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Doxorubicin‐induced DNA intercalation and scavenging by nuclear glutathione S ‐transferase π
Author(s) -
Goto Shinji,
Ihara Yoshito,
Urata Yoshishige,
Izumi Shinichi,
Abe Kuniko,
Koji Takehiko,
Kondo Takahito
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0376com
Subject(s) - doxorubicin , cancer cell , chemistry , cancer , glutathione , cancer research , microbiology and biotechnology , doxorubicin hydrochloride , pharmacology , biochemistry , biology , enzyme , chemotherapy , genetics
Glutathione S‐transferase (GST) functions in xenobiotic biotransformation and drug metabolism. Increased expression of GSTπ, an isozyme of GST, has been found in cancer cells resistant to doxo‐rubicin hydrochloride (DOX) or ci s‐diamminedichloro‐platinum (II) (CDDP), and this increase was believed to be correlated with drug resistance of cancer cells. GST is mainly expressed in the cytoplasm;GSTπ in the nucleus has been reported in cancer cells, but the meaning of this result is not known. Here, we studied changes in the amount of nuclear GSTπ after exposure of cancer cells to anticancer drugs, and role of the nuclear GSTπ in drug resistance. We found nuclear GSTπ in cancer cells resistant to DOX, and the amount of nuclear GSTπ was enhanced by treatment of the cancer cells with DOX or CDDP. We also found that a mushroom lectin, an inhibitor of nuclear transport, inhibited the nuclear transfer of GSTπ, suggesting the existence of a specific transport system for the nuclear transfer of GSTπ. Nuclear GSTπ protected DNA against damage by anticancer drugs. These results suggest a possible role of GSTπ in the acquisition of resistance to anticancer drugs by cancer cells.—Goto, S., Ihara, Y., Urata, Y., Izumi, S., Abe, K., Koji, T., Kondo, T. Doxorubicin‐induced DNA intercalation and scavenging by nuclear glutathione S‐transferase π. FASEB J. 15, 2702–2714 (2001)