Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes

Han Mo Koo, Anne Monks, Andrei Mikheev, Larry V. Rubinstein, Marcia Gray-Goodrich, Mary Jane McWilliams, W. Gregory Alvord, Herbert K. Oie, Adi F. Gazdar, Kenneth D. Paull, Helmut Zarbl, George F. Vande Woude

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Abstract

We used human tumor cell lines from the National Cancer Institute's In Vitro Antineoplastic Drug Screen to assess whether sensitivity to ally of the ~45,000 compounds tested previously correlated with the presence of a ras oncogene. Among these cell lines, the mutations in Ki-ras2 clustered in non- small cell lung and colon carcinoma subpanels, and five of the six leukemia lines contained mutations in either N-ras or Ki-ras2. These analyses revealed a striking correlation with 1-β-D-arabinofuranosylcytosine (Ara-C) and 2,2'- O-cyclocytidine sensitivity in the cell lines harboring ras mutations compared to the tumor lines with wild-type ras alleles. Strong correlations were also found with topoisomerase (topo) II inhibitors, especially 3'- hydroxydaunorubicin and an olivacine derivative. These differential sensitivities persisted in an additional 22 non-small cell lung carcinoma lines (ras mutations, n = 12 and wild-type ras, n = 10). Thus, the association with Ara-C sensitivity was greatest while topo II inhibitors showed a lower, but significant, correlation. These results suggest that the ras oncogene may play a determinant role in rendering tumor cells sensitive to deoxycytidine analogues and topo II inhibitors.

Original languageEnglish (US)
Pages (from-to)5211-5216
Number of pages6
JournalCancer Research
Volume56
Issue number22
StatePublished - Nov 15 1996

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Topoisomerase II Inhibitors
ras Genes
Cytarabine
Tumor Cell Line
Mutation
NSC 284682
Non-Small Cell Lung Carcinoma
Ancitabine
Cell Line
Deoxycytidine
National Cancer Institute (U.S.)
Antineoplastic Agents
Neoplasms
Colon
Leukemia
Alleles

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Koo, H. M., Monks, A., Mikheev, A., Rubinstein, L. V., Gray-Goodrich, M., McWilliams, M. J., ... Vande Woude, G. F. (1996). Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes. Cancer Research, 56(22), 5211-5216.

Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes. / Koo, Han Mo; Monks, Anne; Mikheev, Andrei; Rubinstein, Larry V.; Gray-Goodrich, Marcia; McWilliams, Mary Jane; Alvord, W. Gregory; Oie, Herbert K.; Gazdar, Adi F.; Paull, Kenneth D.; Zarbl, Helmut; Vande Woude, George F.

In: Cancer Research, Vol. 56, No. 22, 15.11.1996, p. 5211-5216.

Research output: Contribution to journalArticle

Koo, HM, Monks, A, Mikheev, A, Rubinstein, LV, Gray-Goodrich, M, McWilliams, MJ, Alvord, WG, Oie, HK, Gazdar, AF, Paull, KD, Zarbl, H & Vande Woude, GF 1996, 'Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes', Cancer Research, vol. 56, no. 22, pp. 5211-5216.
Koo HM, Monks A, Mikheev A, Rubinstein LV, Gray-Goodrich M, McWilliams MJ et al. Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes. Cancer Research. 1996 Nov 15;56(22):5211-5216.
Koo, Han Mo ; Monks, Anne ; Mikheev, Andrei ; Rubinstein, Larry V. ; Gray-Goodrich, Marcia ; McWilliams, Mary Jane ; Alvord, W. Gregory ; Oie, Herbert K. ; Gazdar, Adi F. ; Paull, Kenneth D. ; Zarbl, Helmut ; Vande Woude, George F. / Enhanced sensitivity to 1-β-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes. In: Cancer Research. 1996 ; Vol. 56, No. 22. pp. 5211-5216.
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abstract = "We used human tumor cell lines from the National Cancer Institute's In Vitro Antineoplastic Drug Screen to assess whether sensitivity to ally of the ~45,000 compounds tested previously correlated with the presence of a ras oncogene. Among these cell lines, the mutations in Ki-ras2 clustered in non- small cell lung and colon carcinoma subpanels, and five of the six leukemia lines contained mutations in either N-ras or Ki-ras2. These analyses revealed a striking correlation with 1-β-D-arabinofuranosylcytosine (Ara-C) and 2,2'- O-cyclocytidine sensitivity in the cell lines harboring ras mutations compared to the tumor lines with wild-type ras alleles. Strong correlations were also found with topoisomerase (topo) II inhibitors, especially 3'- hydroxydaunorubicin and an olivacine derivative. These differential sensitivities persisted in an additional 22 non-small cell lung carcinoma lines (ras mutations, n = 12 and wild-type ras, n = 10). Thus, the association with Ara-C sensitivity was greatest while topo II inhibitors showed a lower, but significant, correlation. These results suggest that the ras oncogene may play a determinant role in rendering tumor cells sensitive to deoxycytidine analogues and topo II inhibitors.",
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