Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells

J. K V Willson, B. H. Long, S. Chakrabarty, D. E. Brattain, M. G. Brattain

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Abstract

BMY 25282, a newly designed analogue of mitomycin C (MMC), was assessed for its non-cross-resistant cytotoxic and biochemical action against MMC-resistant human colon carcinoma cells. The analogue has an amidine substituted at position 7 of MMC and has a more efficient intracellular activation to its active species than MMC. In this study we demonstrated that BMY 25282 can overcome MMC resistance in a series of previously described human colon carcinoma cells resistant to MMC (Cancer Res., 44: 5880, 1984). The non-cross-resistance of the analogue in the model was confirmed in vivo by treating tumor xenograft-bearing athymic mice with equitoxic doses of MMC or BMY 25282. We further investigated the formation of interstrand DNA cross-link (IDC) formation by BMY 25282 and MMC. MMC-sensitive cells contained 3 to 8 times as many IDCs as resistant colon carcinoma cells, while no significant differences in IDCs were found between the MMC-sensitive or -resistant cells incubated with BMY 25282. When MMC-sensitive or -resistant cells were exposed to the 70% inhibition concentration or either MMC of BMY 25282, no differences were seen with respect to IDC formation. These studies demonstrate that BMY 25282 is able to overcome MMC resistance in a series of human colon carcinoma cells and that IDC formation in the MMC-sensitive or -resistant cells parallels cytotoxicity for both MMC and analogue.

Original languageEnglish (US)
Pages (from-to)5281-5286
Number of pages6
JournalCancer Research
Volume45
Issue number11 I
StatePublished - 1985

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Mitomycin
Colonic Neoplasms
Colon
Carcinoma
N(6)-((dimethylamino)methylene)mitomycin C
DNA
Amidines
Heterografts
Nude Mice
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Willson, J. K. V., Long, B. H., Chakrabarty, S., Brattain, D. E., & Brattain, M. G. (1985). Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells. Cancer Research, 45(11 I), 5281-5286.

Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells. / Willson, J. K V; Long, B. H.; Chakrabarty, S.; Brattain, D. E.; Brattain, M. G.

In: Cancer Research, Vol. 45, No. 11 I, 1985, p. 5281-5286.

Research output: Contribution to journalArticle

Willson, JKV, Long, BH, Chakrabarty, S, Brattain, DE & Brattain, MG 1985, 'Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells', Cancer Research, vol. 45, no. 11 I, pp. 5281-5286.
Willson JKV, Long BH, Chakrabarty S, Brattain DE, Brattain MG. Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells. Cancer Research. 1985;45(11 I):5281-5286.
Willson, J. K V ; Long, B. H. ; Chakrabarty, S. ; Brattain, D. E. ; Brattain, M. G. / Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells. In: Cancer Research. 1985 ; Vol. 45, No. 11 I. pp. 5281-5286.
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