Sensitization of Cancer Cells to DNA Damaging Agents by Imidazolines

Apoptosis, or programmed cell death, is a cellular mechanism used to regulate cell number and
eliminate damaged or mutated cells. Concomitant with the initiation of the apoptotic cell signal,
chemotherapeutic agents also induce anti-apoptotic factors, such as NF-κB, which compromise the overall
efficacy of chemotherapeutic anticancer treatment. Here we describe an adjuvant therapy in which a small
molecule is used to sensitize cancer cells toward apoptosis induced by chemotherapeutics. Our results
indicate that the imidazoline 1d modulates the pro-survival NF-κB pathway and selectively sensitizes cancer
cells toward DNA damaging agents, thus enhancing the overall efficacy of the treatment. Pretreatment of
cancer cells with the noncytotoxic imidazoline 1d (10 nM) resulted in a significant increase in apoptosis
and anticancer efficacy of the clinically significant DNA damaging agents camptothecin and cisplatin.
Noncancerous cells remained unaffected during this regimen.