Sequence dependent modulation of anticancer drug activities by 7-ethyl-10-hydroxycamptothecin in an HST-1 human squamous carcinoma cell line

N. Masumoto, S. Nakano, T. Esaki, T. Tatsumoto, H. Fujishima, E. Baba, M. Nakamura, Y. Niho

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35 Citations (Scopus)

Abstract

Background: We studied the modulatory effects of 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, on the antitumor activities of clinically important anticancer drugs including cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C (MMC), etoposide (VP-16), and adriamycin (ADR). Materials and Methods: The HST-1 human carcinoma cells were treated with graded concentrations of these anticancer drugs either alone or in combination with IC50 concentration of SN-38, administered in several different treatment schedules, and antitumor activity was evaluated by the growth inhibition assay. Results: SN-38 potentiated the antitumor activity of CDDP in all schedules with a maximal effect observed with a simultaneous administration, while SN-38 enhanced the cytotoxicity of MMC, 5-FU, or VP-16 only in certain schedules. By contrast, SN-38 attenuated the anticancer effect of ADR in all schedules. Conclusions: These results demonstrate that SN-38 may have the advantage of augmenting the anticancer activity in combination with CDDP, MMC, 5-FU, and VP-16, depending on the schedule of administration, and should thus be incorporated into the design of a clinical trial for obtaining maximal therapeutic synergy.

Original languageEnglish
Pages (from-to)405-409
Number of pages5
JournalAnticancer research
Volume15
Issue number2
Publication statusPublished - Jan 1 1995

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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