Exploring the mechanisms of action of FB642 at the cellular level

Lisa A. Hammond, Karen Davidson, Richard Lawrence, James B. Camden, Daniel D. Von Hoff, Steven D Weitman, Elzbieta Izbicka

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

FB642(methyl-2-benzimidazolecarbamate, carbendazim) is a systemic fungicide belonging to the benzimidazole family with antitumor activity against a broad spectrum of tumors both in vitro and in vivo such as pancreas, prostate, colon, and breast. Although the preclinical antitumor activity of FB642 has been well explored, its mechanism of action has not been as well delineated. Previous studies indicate that FB642 may interfere with mitosis and thus may disrupt or inhibit microtubule function resulting in apoptosis. This study seeks to determine if FB642 is a sufficiently novel agent worthy of further development by examining the effect of FB642 on apoptosis, the cell cycle, p53-positive and -negative tumors, and drug-resistant and MDR cell lines. The results of this present study indicate that FB642 increases the degree of apoptosis in all examined tumor cell lines, may induce G2/M uncoupling, may selectively kill p53 abnormal cells, and exhibits antitumor activity in drug- and multidrug-resistant cell lines. The induction of apoptosis by FB642, particularly in p53-deficient cells, its impressive in vivo activity against a broad spectrum of murine and human tumors, as well as an acceptable toxicity profile in animals, make FB642 an excellent candidate for further evaluation in clinical trials in cancer patients.

Original languageEnglish (US)
Pages (from-to)301-313
Number of pages13
JournalJournal of Cancer Research and Clinical Oncology, Supplement
Volume127
Issue number5
StatePublished - 2001

Fingerprint

Apoptosis
Neoplasms
carbendazim
Cell Line
Tumor Cell Line
Mitosis
Microtubules
Pharmaceutical Preparations
Prostate
Pancreas
Cell Cycle
Colon
Breast
Clinical Trials
In Vitro Techniques
benzimidazole

Keywords

  • Benzimidazoles
  • Methyl-2-benzimidazolecarbamate (FB642)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hammond, L. A., Davidson, K., Lawrence, R., Camden, J. B., Von Hoff, D. D., Weitman, S. D., & Izbicka, E. (2001). Exploring the mechanisms of action of FB642 at the cellular level. Journal of Cancer Research and Clinical Oncology, Supplement, 127(5), 301-313.

Exploring the mechanisms of action of FB642 at the cellular level. / Hammond, Lisa A.; Davidson, Karen; Lawrence, Richard; Camden, James B.; Von Hoff, Daniel D.; Weitman, Steven D; Izbicka, Elzbieta.

In: Journal of Cancer Research and Clinical Oncology, Supplement, Vol. 127, No. 5, 2001, p. 301-313.

Research output: Contribution to journalArticle

Hammond, LA, Davidson, K, Lawrence, R, Camden, JB, Von Hoff, DD, Weitman, SD & Izbicka, E 2001, 'Exploring the mechanisms of action of FB642 at the cellular level', Journal of Cancer Research and Clinical Oncology, Supplement, vol. 127, no. 5, pp. 301-313.
Hammond LA, Davidson K, Lawrence R, Camden JB, Von Hoff DD, Weitman SD et al. Exploring the mechanisms of action of FB642 at the cellular level. Journal of Cancer Research and Clinical Oncology, Supplement. 2001;127(5):301-313.
Hammond, Lisa A. ; Davidson, Karen ; Lawrence, Richard ; Camden, James B. ; Von Hoff, Daniel D. ; Weitman, Steven D ; Izbicka, Elzbieta. / Exploring the mechanisms of action of FB642 at the cellular level. In: Journal of Cancer Research and Clinical Oncology, Supplement. 2001 ; Vol. 127, No. 5. pp. 301-313.
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