Exploring the mechanisms of action of FB642 at the cellular level

FBG42(methyl-2-benzimidazolecarbamate, carbendanim) is a systemic fungicide belonging to the benzimidazole family with antitumor activity against a br oad spectrum of tumors both in vitro and in vivo such as pancreas, prostate , colon, and breast. Although the preclinical antitumor activity of FB642 h as been well explored, its mechanism of action has not been as well delinea ted. Previous studies indicate that FB642 may interfere with mitosis and th us 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 l ines. The results of this present study indicate that FB642 increases the d egree of apoptosis in all examined tumor cell lines, may induce G2/M uncoup ling, may selectively kill p53 abnormal cells, and exhibits antitumor activ ity in drug- and multidrug-resistant cell lines. The induction of apoptosis by FB642? particularly in p53-deficient cells, its impressive in vivo acti vity against a broad spectrum of murine and human tumors, as well as an acc eptable toxicity profile in animals, make FB642 an excellent candidate for further evaluation in clinical trials in cancer patients.