Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Sep;85(9):966–971. doi: 10.1111/j.1349-7006.1994.tb02976.x

Synergistic Enhancement of Cisplatin Cytotoxicity by SN‐38, an Active Metabolite of CPT‐11, for Cisplatin‐resistant HeLa Cells

Yukihisa Minagawa 1, Junzo Kigawa 1, Hiroshi Ishihara 1, Hiroaki Itamochi 1, Naoki Terakawa 1,✉
PMCID: PMC5919584  PMID: 7961127

Abstract

A cisplatin (cis‐diamininedichloroplatinuin(II); CDDP)‐resistant HeLa cell line (HeLa/CDDP cells), which showed more than 8‐fold resistance to CDDF compared to the parent cells, was newly established for this study. HeLa/CDDP cells accumulated 50% less platinum than the parent cells. There was no difference in intracellular glutathione (GSH) content between the parent and HeLa/ CDDP cells. The dose modification factor by DL‐buthionine‐S, R‐sulfoximine (BSO) pretreatment was similar in both cell lines. HeLa/CDDP cells had cross‐resistance to diammine (l, l‐cyclobutanedicarboxylato)platinum(II) (CBDCA), (cis‐diammine (glycolato)platinum (254‐S), but not to (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutanedicarboxylato)platinum(II) (DWA2114R), adriamycin, or VP‐16. HeLa/CDDP cells showed a collateral sensitivity to 7‐ethyl‐10‐hydroxycampto‐thecin (SN‐38), an active metabolite of 7‐ethyl‐10‐[4‐(l‐piperidino)‐l‐piperidino]carbonyloxycamptothecin (CPT‐11). Furthermore, isobologram analysis indicated synergistic interaction of CDDP and SN‐38 only for HeLa/CDDP cells. The present study suggests that combination therapy with CDDP and CPT‐11 may he potentially useful in the treatment of some patients with CDDP‐resistant cancer.

Keywords: CDDP, resistance, CPT‐11, HeLa cell

Full Text

The Full Text of this article is available as a PDF (322.2 KB).

REFERENCES

  • 1. ) Loehrer , P. J. and Einhorn , L. H.Cisplatin , Ann. Int. Med , 100 , 704 – 713 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Ozols , R. F. and Young , R. C.Chemotherapy of ovarian cancer . Semin. Oncol , 11 , 251 – 263 ( 1984. ). [PubMed] [Google Scholar]
  • 3. ) Scanlon , K. J. , Kashani‐Sabet , M. , Miyachi , H. , Sowers , L. C. and Rossi , J.Molecular basis of cisplatin resistance in human carcinomas: model systems and patients . Anticancer Res , 9 , 1301 – 1312 ( 1989. ). [PubMed] [Google Scholar]
  • 4. ) Andrews , P. A. and Ho Well , S. B.Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance . Cancer Cells , 2 , 35 – 43 ( 1990. ). [PubMed] [Google Scholar]
  • 5. ) Drlica , K. and Franco , R. J.Inhibitors of DNA topoisomerases . Biochemistry , 27 , 2253 – 2259 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Schabel , F. M.Jr. , Trader , M. W. , Laster , W. R. , Jr. , Corbett , T. H. and Griswold , D. P. , Jr.cis‐Dichlorodiammineplatinum(II): combination chemotherapy and cross‐resistance studies with tumors of mice . Cancer Treat. Rep , 63 , 1459 – 1473 ( 1979. ). [PubMed] [Google Scholar]
  • 7. ) Sculier , J. P. and Klastersky , J.Progress in chemotherapy for non‐small cell lung cancer . Eur. J. Cancer Clin. Oncol , 20 , 1329 – 1333 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Hsiang , Y.‐H. and Liu , L. F.Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin . Cancer Res , 48 , 1722 – 1726 ( 1988. ). [PubMed] [Google Scholar]
  • 9. ) Hertzberg , R. P. , Caranfa , M. J. and Hecht , S. M.On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme‐DNA complex . Biochemistry , 28 , 4629 – 4638 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Kunimoto , T. , Nitta , K. , Tanaka , T. , Uehara , N. , Baba , H. , Takeuchi , M. , Yokokura , T. , Sawada , S. , Miyasaka , T. and Mutai , M.Antitumor activity of 7‐ethyl‐10‐[4‐(1‐piperidino) ‐1 ‐piperidino]carbonyloxycamptothecin, a novel water‐soluble derivative of camptothecin, against murine tumors . Cancer Res , 47 , 5944 – 5947 ( 1987. ). [PubMed] [Google Scholar]
  • 11. ) Tsuruo , T. , Matsuzaki , T. , Matsushita , M. , Saito , H. and Yokokura , T.Antitumor effect of CPT‐11, a new derivative of camptothecin, against pleiotropic drug‐resistant tumors in vitro and in vivo . Cancer Chemotker. Pharmacol , 21 , 71 – 74 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Kaneda , K , Nagata , H. , Furuta , T. and Yokokura , T.Metabolism and pharmacokinetics of the camptothecin analogue CPT‐11 in the mouse . Cancer Res , 50 , 1715 – 1720 ( 1990. ). [PubMed] [Google Scholar]
  • 13. ) Kawato , Y. , Aonuma , M. , Hirota , Y. , Kuga , H. and Sato , K.Intracellular roles of SN‐38, a metabolite of the camptothecin derivative CPT‐11, in the antitumor effect of CPT‐11 . Cancer Res , 51 , 4187 – 4191 ( 1991. ). [PubMed] [Google Scholar]
  • 14. ) Kano , Y. , Suzuki , K. , Akutsu , M. , Suda , K. , Inoue , Y. , Yoshida , M. , Sakamoto , S. and Miura , Y.Effects of CPT‐11 in combination with other anti‐cancer agents in culture . Int. J. Cancer , 50 , 604 – 610 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Masuda , N. , Fukuoka , M. , Takada , M. , Kusunoki , Y. , Negoro , S. , Matsui , K. , Kudoh , S. , Takifuji , N. , Nakagawa , K. and Kishimoto , S.CPT‐11 in combination with cisplatin for advanced non‐small‐cell lung cancer . J. Clin. Oncol. , 10 , 1775 – 1780 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) LeRoy , A. F. , Wehling , M. L. , Sponseller , H. L. , Friauf , W. S. , Solomon , R. E. , Dedrick , R. L. , Litterst , C. L. , Gram , T. E. , Guarino , A. M. and Becker , D. A.Analysis of platinum in biological materials by flameless atomic absorption spectrophotometry . Biochem, Med , 18 , 184 – 191 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Griffith , O. W.Determination of glutathione and glutathione disulfide using glutathione reductase and 2‐vinyl‐pyridine . Anal. Biochem , 106 , 207 – 212 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Green , J. A. , Vistica , D. T. , Young , R. C. , Hamilton , T. C. , Rogan , A. M. and Ozols , R. F.Potentiation of melphalan cytotoxicity in human ovarian cell lines by glutathione depletion . Cancer Res , 44 , 5427 – 5431 ( 1984. ). [PubMed] [Google Scholar]
  • 19. ) Lowry , O. H. , Rosebrough , N. J. , Farr , A. L. and Randall , R. J.Protein measurement with the Folin phenol reagent . J. Biol. Chem , 193 , 265 – 269 ( 1951. ). [PubMed] [Google Scholar]
  • 20. ) Mosmann , T.Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays . J. Immunol Methods , 65 , 55 – 63 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Kano , Y. , Ohnuma , T. , Okano , T. and Holland , J. F.Effect of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture . Cancer Res , 48 , 351 – 356 ( 1988. ). [PubMed] [Google Scholar]
  • 22. ) Chao , C. C.‐K. , Lee , Y.‐L. , Cheng , P.‐W. and Lin‐Chao , S.Enhanced host cell reactivation of damaged plasmid DMA in HeLa cells resistant to cis‐diamminedichloro‐platinum(II) . Cancer Res , 51 , 601 – 605 ( 1991. ). [PubMed] [Google Scholar]
  • 23. ) Shelagh , E. L. , Gerlach , J. H. and Cole , S. P. C.Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin . Cancer Res , 47 , 2594 – 2598 ( 1987. ). [PubMed] [Google Scholar]
  • 24. ) Misawa , T. , Kikkawa , F. , Oguchi , H. , Morikawa , Y. , Kawai , M. , Maeda , O. , Iwata , M. , Kano , T. , Furuhashi , Y. and Tomoda , Y.Accumulation of cis‐diamminedichloroplatinum(II) and its analogues in sensitive and resistant human ovarian carcinoma cells . Oncology , 49 , 173 – 179 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Masuda , N. , Fukuoka , M. , Kusunoki , Y. , Matsui , K. , Takifuji , N. , Kudoh , S. , Negoro , S. , Nishioka , M. , Nakagawa , K. and Takada , M.CPT‐11: a new derivative of camptothecin for the treatment of refractory or relapsed small‐cell lung cancer . J. Clin. Oncol. , 10 , 1225 – 1229 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Niimi , S. , Nakagawa , K. , Sugimoto , Y. , Nishio , K. , Fujiwara , Y. , Yokoyama , S. , Terashima , Y. and Saijo , N.Mechanism of cross‐resistance to camptothecin analogue (CPT‐11) in a human ovarian cancer cell line selected by cisplatin . Cancer Res , 52 , 328 – 333 ( 1992. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES