Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Feb;89(2):199–205. doi: 10.1111/j.1349-7006.1998.tb00549.x

Suppression of Anti‐microtubule Agent‐induced Apoptosis by Nitric Oxide: Possible Mechanism of a New Drug Resistance

Tsutomu Ogura 1,✉, George DeGeorge 1,†, Masayuki Tatemichi 1, Hiroyasu Esumi 1
PMCID: PMC5921764  PMID: 9548448

Abstract

The propensity of a cell to undergo apoptosis has been proposed to be a determinant of sensitivity to anti‐microtubule agents. The anti‐microtubule agents vincristine and paclitaxel induce key features of apoptosis, such as intranucleosomal DNA fragmentation and changes in nuclear morphology in the human neuroblastoma cell line, NB‐39‐nu. Nitric oxide (NO) generated from NO‐releasing drugs prevented anti‐microtubule agent‐induced apoptosis in this cell line. The mechanism of suppression of apoptosis by NO appears to be via the inhibition of an interleukin‐1β converting enzyme‐like protease cascade. This finding reveals a new biological function of NO, as well as a new molecular insight into resistance to chemotherapy with anti‐microtubule agents.

Keywords: Nitric oxide, Apoptosis, Anti‐microtubule agent, ICE protease cascade

Full Text

The Full Text of this article is available as a PDF (363.5 KB).

REFERENCES

  • 1. ) Moscow , J. A. and Cowan , K. H. J.Multidrug resistance . J. Natl. Cancer Inst. , 80 , 14 – 20 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Fojo , A. T. , Ueda , K. , Slamon , D. J. , Poplack , D. G. , Gottesman , M. M. and Pastan , I.Expression of multidrug‐resistance gene in human tumors and tissues . Proc. Natl. Acad. Sci. USA , 84 , 265 – 269 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Brewer , F. and Warr , J. R.Verapamil reversal of vincristine resistance and cross‐resistance patterns of vincristine‐resistant Chinese hamster ovary cells . Cancer Treat. Rep. , 71 , 353 – 359 ( 1987. ). [PubMed] [Google Scholar]
  • 4. ) Da , S. C. , De , O. C. , Da , C. M. and De , L. P.Apoptosis as a mechanism of cell death induced by different chemotherapeutic drugs in human leukemic T‐lymphocytes . Biochem. Pharmacol. , 55 , 1331 – 1340 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Geyp , M. , Ireland , C. M. and Pittman , S. M.Resistance to apoptotic cell death in a drug resistant T cell leukaemia cell line . Leukemia , 10 , 447 – 455 ( 1996. ). [PubMed] [Google Scholar]
  • 6. ) Gangemi , R. M. , Tiso , M. , Marchetti , C. , Severi , A. B. and Fabbi , M.Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death . Cancer Chemother. Pharm. , 36 , 385 – 392 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Messmer , U. K. , Lapetina , E. G. and Brune , B.Nitric oxide‐induced apoptosis in RAW 264.7 macrophages is antagonized by protein kinase C‐ and protein kinase A‐activating compounds . Mol. Pharmacol. , 47 , 757 – 765 ( 1995. ). [PubMed] [Google Scholar]
  • 8. ) Ankarcrona , M. , Dypbukt , J. M. , Brune , B. and Nicotera , P.Interleukin‐1 beta‐induced nitric oxide production activates apoptosis in pancreatic RINm5F cells . Exp. Cell Res. , 213 , 172 – 177 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Blanco , F. J. , Ochs , R. L. , Schwarz , H. and Lotz , M.Chondrocyte apoptosis induced by nitric oxide . Am. J. Pathol. , 146 , 75 – 85 ( 1995. ). [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Fehsel , K. , Kroncke , K.‐D. , Meyer , K. L. , Huber , H. , Wahn , V. and Kolb‐Bachofen , V.Nitric oxide induces apoptosis in mouse thymocytes . J. Immunol. , 155 , 2858 – 2865 ( 1995. ). [PubMed] [Google Scholar]
  • 11. ) Farinelli , S. E. , Park , D. S. and Greene , L. A.Nitric oxide delays the death of trophic factor‐deprived PC12 cells and synpathetic neurons by a cGMP‐mediated mechanism . J. Neurosci. , 16 , 2325 – 2334 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Mannick , J. B. , Asano , K. , Izumi , K. , Kieff , E. and Stamler , J. S.Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein‐Barr virus reactivation . Cell , 79 , 1137 – 1146 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Dimmeler , S. , Haendeler , J. , Nehls , M. and Zeiher , A. M.Suppression of apoptosis by nitric oxide via inhibition of interleukin‐1β‐converting enzyme (ICE)‐like and cysteine protease protein (CPP)‐32‐like proteases . J. Exp. Med. , 185 , 601 – 607 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Ikeda , I. , Ishizaka , Y. , Tahira , T. , Suzuki , T. , Onda , M. , Sugimura , T. and Nagao , M.Specific expression of the ret proto‐oncogene in human neuroblastoma cell lines . Oncogene , 5 , 1291 – 1296 ( 1990. ). [PubMed] [Google Scholar]
  • 15. ) Davis , L. G. , Dibner , M. D. and Battey , J. F.DNA preparation from cultured cells and tissue . In“Methods in Molecular Biology ,” ed. Davis L. G. , Dibner M. D. and Battey J. F. , pp. 44 – 46 ( 1986. ). Elsevier; , New York . [Google Scholar]
  • 16. ) Enari , M. , Talanian , R. V. , Wong , W. W. and Nagata , S.Sequential activation of ICE‐like and CPP32‐like proteases during Fas‐mediated apoptosis . Nature , 380 , 723 – 726 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Ogura , T. , Takenouchi , N. , Yamaguchi , M. , Matsukage , A. , Sugimura , T. and Esumi , H.Striking similarity of the distribution patterns of the poly(ADP‐ribose) polymerase and DNA polymerase β among various mouse organs . Biochem. Biophys. Res. Commun. , 172 , 377 – 384 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Schmidt , H. H. H. W. , Lohmann , S. M. and Walter , U.The nitric oxide and cGMP signal transduction system: regulation and mechanism of action . Biochim. Biophys. Acta , 1178 , 153 – 175 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Chang , Y. F. , Li , L. L. , Wu , C. W. , Liu , T. Y. , Lui , W. Y. , Peng , F. K. and Chi , C. W.Paclitaxel‐induced apoptosis in human gastric carcinoma cell line . Cancer , 77 , 14 – 18 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Danesi , R. , Figg , W. D. , Reed , E. and Myers , C. E.Paclitaxel (Taxol) inhibits protein isoprenylation and induces apoptosis in PC‐3 human prostate cancer cells . Mol. Pharmacol. , 47 , 1106 – 1111 ( 1995. ). [PubMed] [Google Scholar]
  • 21. ) Havrilesky , L. J. , Elbendary , A. , Hurteau , L. A. , Whitaker , R. S. , Rodriguez , G. C. and Berchuck , A.Chemotherapy‐induced apoptosis in epithelial ovarian cancers . Obstet. Gynecol. , 85 , 1007 – 1010 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Martin , S. J. and Green , D. R.Protease activation during apoptosis: death by a thousand cuts ? Cell , 82 , 349 – 352 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Kaufmann , S. H. , Desnoyers , S. , Ottaviano , Y. , Davidson , N. E. and Poirier , G. G.Specific proteolytic cleavage of poly(ADP‐ribose) polymerase: an early marker of chemotherapy‐induced apoptosis . Cancer Res. , 53 , 3976 – 3985 ( 1993. ). [PubMed] [Google Scholar]
  • 24. ) Tewari , M. , Quan , L. T. , O'Rourke , K. , Desnoyers , S. , Zeng , Z. , Beidler , D. R. , Poirier , G. G. , Salvesen , G. S. and Dixit , V. M.Yama/CPP32β, a mammalian homolog of CED‐3, is a crmA‐inhibitable protease that cleaves the death substrate poly(ADP‐ribose) polymerase . Cell , 81 , 801 – 809 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Bender , R. A. , Hamel , E. and Hande , K. R.The plant alkaloids . In“Cancer Chemotherapy: Principles and Practice ,” ed. Chabner B. A. and Collins J. M. , pp. 253 – 275 ( 1990. ). Lippincott; , Philadelphia . [Google Scholar]
  • 26. ) Burris , H. A. , 3rd and Fields , S.Summary of data from in vitro and phase I vinorelbine (Navelbine) . Semin. Oncol. , 21 , 14 – 19 ( 1994. ). [PubMed] [Google Scholar]
  • 27. ) Spencer , C. M. and Faulds , D.Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer . Drugs , 48 , 794 – 847 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Fraser , A. and Evan , G.A license to kill . Cell , 85 , 781 – 784 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Fisher , D. E.Apoptosis in cancer therapy: crossing the threshold . Cell , 78 , 539 – 542 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Stamler , J. S.Redox signaling: nitrosylation and related target interactions of nitric oxide . Cell , 78 , 931 – 936 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Ogura , T. , Tatemichi , M. and Esumi , H.Nitric oxide inhibits CPP32‐like activity under redox regulation . Biochem. Biophys. Res. Commun. , 236 , 365 – 369 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Miyashita , T. and Reed , J. C.bcl‐2 gene transfer increases relative resistance of S49.1 and WEHI7.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs . Cancer Res. , 52 , 5407 – 5411 ( 1992. ). [PubMed] [Google Scholar]
  • 33. ) Tang , C. , Willingham , M. C. , Reed , J. C. , Miyashita , T. , Ray , S. , Ponnathpur , V. , Huang , Y. , Mahoney , M. E. , Bullock , G. and Bhalla , K.High levels of p26BCL‐2 oncoprotein retard taxol‐induced apoptosis in human pre‐B leukemia cells . Leukemia , 8 , 1960 – 1969 ( 1994. ). [PubMed] [Google Scholar]
  • 34. ) Liu , X. , Kim , C. N. , Yang , J. , Jemmerson , R. and Wang , X.Induction of apoptosis program in cell‐free extracts: requirement for dATP and cytochrome c . Cell , 86 , 147 – 157 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 35. ) Yang , J. , Liu , X. , Bhalla , K. , Kim , C. N. , Ibrado , A. M. , Cai , J. , Peng , T.‐I. , Jones , D. P. and Wang , X.Prevention of apoptosis by Bcl‐2: release of cytochrome c from mitochondria blocked . Science , 275 , 1129 – 1132 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 36. ) Kluck , R. M. , Bossy‐Wetzel , E. , Green , D. R. and Newmeyer , D. D.The release of cytochrome c from mitochondria: a primary site for Bcl‐2 regulation of apoptosis . Science , 275 , 1132 – 1136 ( 1997. ). [DOI] [PubMed] [Google Scholar]

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

RESOURCES