How bleomycin cuts cancer to pieces

In the first case—where bleomycin achieves single strand cleavage—the bleomycin molecule can then become reactivated, once more abstracting a hydrogen atom from the opposing DNA strand.

The opposite strand can again follow 1 of 2 pathways, (a) full cleavage of the opposing strand, yielding a double-strand cleavage or (b) formation of an AP site. The researchers noted that this AP site can lead to strand cleavage through the opposing DNA strand with the addition of a mild base like n-butylamine.

The results of this study emphasize the correlation between the strength of bleomycin binding to DNA and the frequency of double-strand cleavage. Of the 10 sample hairpin DNAs, the 2 most tightly bound to bleomycin each showed 5 double-strand cleavages, whereas the least tightly bound samples exhibited just 2 double-strand cleavages.

This suggests a plausible mechanism for DNA cleavage by bleomycin that may lead to tumor cell killing, as well as identifying the most common sequences involved in DNA site binding and subsequent strand breakage.

Roy noted, however, that more research is needed to elucidate the biochemical causes of tight binding by bleomycin. Furthermore, bleomycin’s specificity for cancer cells remains enigmatic.

“Cancer is still a black hole,” Roy said. “We’re trying to make this particular molecule better. There is still so much to learn.”