The role of glucuronidation in 7-ethyl-10-hydroxycamptothecin resistance in vitro

Toshiaki Takahashi, Yasuhiro Fujiwara, Michio Yamakido, Osamu Katoh, Hiromitsu Watanabe, Peter I. Mackenzie

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    Abstract

    Although glucuronidation catalyzed by uridine 5'-diphosphoglucuronosyltransferase (UGT) is a major pathway of drug inactivation in humans, glucuronidation in malignant cells has received little attention as a cause of anti-cancer drug resistance. In this study, we tried to elucidate the role of SN-38 glucuronidation in the CPT-11-resistant human lung cancer cell line PC-7/CPT. PC-7/CPT cells possessed an increased activity to glucuronidate SN-38 compared to the parent cells, PC-7. Furthermore, sensitivity of PC-7/CPT cells to SN-38 was improved by inhibiting UGT activity. Western and northern blot analyses demonstrated that this increased activity was due to increased levels of UGT protein and mRNA. These results not only imply that upregulation of UGT activity in PC-7/CPT cells may contribute in part to SN-38 resistance, but also illustrate the importance of drug metabolism within malignant cells themselves, as a cause of drug resistance.

    Original languageEnglish
    Pages (from-to)1211-1217
    Number of pages7
    JournalJapanese Journal of Cancer Research
    Volume88
    Issue number12
    DOIs
    Publication statusPublished - 1 Jan 1997

    Keywords

    • CPT-11
    • Drug resistance
    • Lung cancer
    • SN-38
    • UDP-glucuronosyltransferase

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